c-peptide and Albuminuria

Topics: Albuminuria; Animals; Biomarkers; C-Peptide; Calmodulin; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glomerular Filtration Rate; Humans; Insulin; Insulin-Secreting Cells; Metabolic Syndrome; Receptors, G-Protein-Coupled; Sodium-Potassium-Exchanging ATPase

Of the many information obtainable from the urine of diabetic patients, urinary C-peptide (CPR), albumin and anti-diuretic hormone (ADH) were representatively described using my clinical and experimental data. C-peptide excretion in 24h collection of urine is a good estimate of insulin secretion from the pancreas and thus low in IDDM patients and even in NIDDM patients at a later stage, but high in pathological conditions including Graves' disease, obesity, liver cirrhosis and Cushing's syndrome. Urinary albumin excretion in small amounts (microalbuminuria) is usually observed in diabetic patients who have been under a poor control state of diabetic hyperglycemia for over 5 years and provides a good tool for monitoring early diabetic nephropathy. The grade of microalbuminuria (30-300 mg/day) is positively correlated with the HbA1 level in diabetic patients, showing that microalbuminuria is reversible along with an improvement of diabetic control at least in an early phase of diabetic nephropathy. As the albumin level measured in a spot urine sample correlates well with the value in the 24h collection of urine, the albumin measurement is conveniently feasible with a spot urine sample at every patient's visit. The amount of ADH excreted in urine is 7-10% of that secreted from the posterior pituitary. The excretion of ADH in a day was in the urine of diabetic patients positively correlated with HbA1, urinary osmolarity and concentration of sodium in urine, although the pathological meaning of the observed ADH hypersecretion in the development of diabetic complications is currently unknown.

Topics: Albuminuria; C-Peptide; Diabetes Complications; Diabetes Mellitus; Humans; Vasopressins

Type II diabetes is a frequent disease among older people (approximately 7% of 60-year-olds in the US). Genetic factors play a more important role in the etiology of type II than of type I diabetes. The metabolic derangements of type II diabetes are due to the combination of a diminished effect of insulin (insulin resistance due to a decreased number of insulin receptors and a postreceptor defect the nature of which is not clear) and a disturbance of insulin secretion. Type II diabetes is associated with a more than doubling of the age-specific mortality, mainly due to diabetic macroangiopathy (myocardial infarctions, cerebrovascular insults). Diet remains the basis of treatment for type II diabetes. The composition of the diet, however, has been altered in that the proportion of carbohydrates has been increased, the proportion of fat decreased and the fibre content increased. If necessary, oral antidiabetics or insulin are added to the dietary treatment. Measurement of C-peptide may help to decide when insulin therapy is required. Measuring HbA1c permits assessment of the mean blood sugar value of the last 1 1/2-2 months. The greatest progress recently made in the treatment of the chronic complications of type II diabetes has been in the field of diabetic retinopathy (photocoagulation for retinopathy lesions, vitrectomy).

Topics: Aged; Aging; Albuminuria; C-Peptide; Combined Modality Therapy; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Exercise; Glycated Hemoglobin; Humans; Insulin; Insulin Secretion; Middle Aged

There is a traditional belief in the Middle East that regular consumption of camel milk may aid in prevention and control of diabetes. The aim of this work was to evaluate the efficacy of camel milk as an adjuvant therapy in young type 1 diabetics. This 16-week randomized study enrolled 54 type 1 diabetic patients (average age 20 years) selected from those attending the outpatient diabetes clinic of the Menofia University Hospital, affiliated with Egypt's National Cancer Institute. Subjects were randomly divided into two groups of 27 patients: one received usual management (diet, exercise, and insulin), whereas the other received 500 mL of camel milk daily in addition to standard management. A control group of 10 healthy subjects was also assessed. The following parameters were evaluated at baseline and at 4 and 16 weeks: hemoglobin A1c (HbA1c), human C-peptide, lipid profile, serum insulin, anti-insulin antibodies, creatinine clearance, albumin in 24-hour urine, body mass index, and Diabetes Quality of Life score. The following parameters were significantly different between the usual-management group versus the camel milk group after 16 weeks: fasting blood sugar (227.2 +/- 17.7 vs. 98.9 +/- 16.2 mg/dL), HbA1c (9.59 +/- 2.05[%] vs. 7.16 +/- 1.84[%]), serum anti-insulin antibodies (26.20 +/- 7.69 vs. 20.92 +/- 5.45 microU/mL), urinary albumin excretion (25.17 +/- 5.43 vs. 14.54 +/- 5.62 mg/dL/24 hours), daily insulin dose (48.1 +/- 6.95 vs. 23 +/- 4.05 units), and body mass index (18.43 +/- 3.59 vs. 24.3 +/- 2.95 kg/m(2)). Most notably, C-peptide levels were markedly higher in the camel milk group (0.28 +/- 0.6 vs. 2.30 +/- 0.51 pmol/mL). These results suggest that, as an adjunct to standard management, daily ingestion of camel milk can aid metabolic control in young type 1 diabetics, at least in part by boosting endogenous insulin secretion.

Topics: Adolescent; Adult; Albuminuria; Animals; Autoantibodies; Blood Glucose; Body Mass Index; C-Peptide; Camelus; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Insulin; Insulin Secretion; Medicine, Traditional; Middle East; Milk; Young Adult

One year survival of islet cell grafts has been reproducibly achieved under combination immune therapy including tacrolimus (TAC). However, the use of TAC causes beta-cell and renal toxicity. Because sirolimus (SIR) monotherapy was successful in kidney transplantation under antithymocyte globulin (ATG), we undertook a pilot study comparing SIR monotherapy with SIR-TAC combination therapy.. Nonuremic type 1 diabetics received a cultured beta-cell graft under ATG and were randomly assigned to SIR or SIR-TAC-maintenance therapy; a second graft was implanted during posttransplantation month 3 without ATG. The planned number of patients per group (n=10) was reduced to five in view of the observed side effects.. At posttransplant month 6, three SIR-patients had lost graft function and two presented marginal function; among SIR-TAC-patients, there were two early graft failures but three became insulin-independent. These three patients maintained metabolically relevant function (C-peptide >1 ng/ml and coefficient of variation fasting glycemia <25%) for more than 2 years but low-dose insulin therapy was needed from 8, 18, and 26 months posttransplant; this was still the case in two of them after reducing and stopping TAC dose. In both groups, incapacitating adverse events were attributed to sirolimus requiring its discontinuation in 4 of 10 patients; in the 3 patients with pretransplant microalbuminuria, macroalbuminuria developed which resolved when sirolimus was stopped.. SIR monotherapy is not sufficient to suppress rejection after transplantation under ATG, but it can maintain survival of established beta-cell grafts. However, the risk for a SIR-induced proteinuria remains a concern.

Topics: Adult; Albuminuria; Autoantibodies; C-Peptide; Cell Transplantation; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Female; Graft Survival; Humans; Immunosuppressive Agents; Islets of Langerhans; Islets of Langerhans Transplantation; Lymphocyte Count; Male; Middle Aged; Postoperative Complications; Sirolimus; Tacrolimus

The aim of the present cross-sectional study was to investigate the relationship between urinary albumin excretion and insulin sensitivity, intact insulin and insulin propeptides in 104 clinically healthy 58-year-old men recruited from the general population. Insulin sensitivity (hyperinsulinemic euglycemic clamp) adjusted for lean body mass, fasting plasma insulin, proinsulin, split-proinsulin, C-peptide, and urinary albumin excretion and were determined. Urinary albumin excretion was significantly associated with body mass index (BMI), systolic and diastolic blood pressure, plasma insulin, and C-peptide (P <.05). Insulin sensitivity tended to be associated with urinary albumin excretion (P=.07). In a multiple regression analysis, urinary albumin excretion was independently and significantly associated with systolic blood pressure (P <.05). In conclusion, urinary albumin excretion was associated with insulin and C-peptide in clinically healthy 58-year-old men; however, this relationship became insignificant when blood pressure was taken into account in the regression analysis.

Topics: Albuminuria; Blood Pressure; Body Mass Index; C-Peptide; Cross-Sectional Studies; Diastole; Glucose Clamp Technique; Humans; Insulin; Male; Middle Aged; Proinsulin; Reference Values; Regression Analysis; Sweden; Systole

Recent studies have indicated that proinsulin C-peptide shows specific binding to cell membrane binding sites and may exert biological effects when administered to patients with Type 1 diabetes mellitus. This study was undertaken to determine if combined treatment with C-peptide and insulin might reduce the level of microalbuminuria in patients with Type 1 diabetes and incipient nephropathy.. Twenty-one normotensive patients with microalbuminuria were studied for 6 months in a double-blind, randomized, cross-over design. The patients received s.c. injections of either human C-peptide (600 nmol/24 h) or placebo plus their regular insulin regimen for 3 months.. Glycaemic control improved slightly during the study and to a similar extent in both treatment groups. Blood pressure was unaltered throughout the study. During the C-peptide treatment period, urinary albumin excretion decreased progressively on average from 58 microg/min (basal) to 34 microg/min (3 months, P < 0.01) and it tended to increase, but not significantly so, during the placebo period. The difference between the two treatment periods was statistically significant (P < 0.01). In the 12 patients with signs of autonomic neuropathy prior to the study, respiratory heart rate variability increased by 21 +/- 9% (P < 0.05) during treatment with C-peptide but was unaltered during placebo. Thermal thresholds were significantly improved during C-peptide treatment in comparison to placebo (n = 6, P < 0.05).. These results indicate that combined treatment with C-peptide and insulin for 3 months may improve renal function by diminishing urinary albumin excretion and ameliorate autonomic and sensory nerve dysfunction in patients with Type 1 diabetes mellitus.

Topics: Adult; Albuminuria; Autonomic Nervous System Diseases; Blood Glucose; C-Peptide; Cross-Over Studies; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Diabetic Neuropathies; Double-Blind Method; Heart Rate; Humans; Insulin; Kidney; Placebos

Compared with other insulin regimens, combination therapy with oral hypoglycemic agents and bedtime insulin produces similar improvement in glycemic control but induces less weight gain.. To determine whether bedtime insulin regimens differ with respect to their effects on weight gain in patients with type 2 diabetes.. Randomized, controlled trial.. Four outpatient clinics at central hospitals.. 96 patients (mean age, 58 +/- 1 years; mean body mass index, 29 +/- 1 kg/m2) whose type 2 diabetes was poorly controlled with sulfonylurea therapy (mean glycosylated hemoglobin value, 9.9% +/- 0.2%; mean fasting plasma glucose level, 11.9 +/- 0.3 mmol/L [214 +/- 5 mg/dL]).. Random assignment to 1 year of treatment with bedtime intermediate-acting insulin plus glyburide (10.5 mg) and placebo, metformin (2 g) and placebo, glyburide and metformin, or a second injection of intermediate-acting insulin in the morning. Patients were taught to adjust the bedtime insulin dose on the basis of fasting glucose measurements.. Body weight, biochemical and symptomatic hypoglycemias, and indices of glycemic control.. At 1 year, body weight remained unchanged in patients receiving bedtime insulin plus metformin (mean change, 0.9 +/- 1.2 kg; P < 0.001 compared with all other groups) but increased by 3.9 +/- 0.7 kg, 3.6 +/- 1.2 kg, and 4.6 +/- 1.0 kg in patients receiving bedtime insulin plus glyburide, those receiving bedtime insulin plus both oral drugs, and those receiving bedtime and morning insulin, respectively. The greatest decrease in the glycosylated hemoglobin value was observed in the bedtime insulin and metformin group (from 9.7% +/- 0.4% to 7.2% +/- 0.2% [difference, -2.5 +/- 0.4 percentage points] at 1 year; P < 0.001 compared with 0 months and P < 0.05 compared with other groups). This group also had significantly fewer symptomatic and biochemical cases of hypoglycemia (P < 0.05) than the other groups.. Combination therapy with bedtime insulin plus metformin prevents weight gain. This regimen also seems superior to other bedtime insulin regimens with respect to improvement in glycemic control and frequency of hypoglycemia.

Topics: Albuminuria; Blood Glucose; Blood Pressure; C-Peptide; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Follow-Up Studies; Glyburide; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Lipids; Metformin; Middle Aged; Weight Gain

Children (n = 38) aged 3-15 y were randomly chosen, at the time of diabetes diagnosis, for conventional management at a hospital ward, or for treatment partly in a training apartment where the family was offered problem-based education and special therapeutic support. HbA1c, blood glucose stability, urinary C-peptide excretions and incidence of hypoglycaemic attacks and diabetes ketoacidosis (DKA) were monitored and some standardized, self-estimated psychological tests were performed during the first 2 y after diagnosis. During the 3 y thereafter, HbA1c, presence of DKA, microalbuminuria, retinopathy and hypertension were monitored. None of the patients demonstrated signs of diabetes microangiopathy or DKA. The overall mean HbA1c level was 7.2% 5 y after diagnosis and 30% of the children had HbA1c values <6.3%. There were no differences in the HbA1c values for the patients treated by the different management regimens. Blood glucose variability (SD) was also similar, with 75% of the values in the range of 3-10 mmol/l. Patients with poor glycaemic control (mean HbA1c >8.3%) year 5 after diagnosis had already the second year after diagnosis significantly higher HbA1c values and blood glucose variability. The fathers of these patients demonstrated a higher degree of maladjustment. On the basis of increasing HbA1c values, high blood glucose variability and psychosocial risk factors such as their fathers' emotional responses, patients at risk for poor metabolic control in the future can be identified within 2 y after diagnosis. Efforts and resources can thus be focused at an early stage on this group.

Topics: Adaptation, Psychological; Adolescent; Albuminuria; Analysis of Variance; Attitude to Health; Blood Glucose; C-Peptide; Chi-Square Distribution; Child; Child, Preschool; Chromatography, High Pressure Liquid; Diabetes Mellitus, Type 1; Family Therapy; Fathers; Female; Glycated Hemoglobin; Humans; Insulin; Male; Patient Education as Topic; Radioimmunoassay; Risk Factors; Statistics, Nonparametric; Sweden

Although some studies have suggested a direct action of troglitazone on vascular cells, its effects on diabetic vascular diseases have not been reported. We therefore investigated the effect of troglitazone on microalbuminuria in patients with incipient diabetic nephropathy.. A total of 30 patients with type 2 diabetes associated with microalbuminuria (urinary albumin-to-creatinine ratio [ACR] [milligrams per gram creatinine] ranging from 30 to 300 mg/g creatinine) were studied. They were randomly divided into two groups: patients treated with metformin (500 mg/day, n = 13) or with troglitazone (400 mg/day, n = 17) for 12 weeks. ACR, lipid profile, blood pressure, glycated hemoglobin, and plasma glucose during meal-load tests were measured every 4 weeks.. Anthropometric indices (BMI and percent fat), lipid profile, and blood pressure did not change with either treatment. Fasting and postmeal glucose levels decreased similarly in the two groups. Decrements in glycated hemoglobin were greater in the metformin group at 4 and 8 weeks after the initiation of treatment (P < 0.05). Troglitazone reduced ACR (median [25-75th percentiles]) from 70 (49-195) to 40 (31-90) mg/g creatinine at 4 weeks (P = 0.021) and maintained these reduced levels throughout the treatment period (8 weeks: 35 [26-68], P = 0.007; 12 weeks: 43 [26-103], P = 0.047). Metformin did not change ACR throughout the 12 weeks.. Troglitazone ameliorated microalbuminuria in diabetic nephropathy. Furthermore, our findings suggest that troglitazone has some effects on vascular cells other than lowering plasma glucose levels. Troglitazone might be useful for diabetic angiopathy, including nephropathy and coronary artery disease.

Topics: Aged; Albuminuria; Blood Glucose; Blood Pressure; C-Peptide; Cholesterol; Cholesterol, HDL; Chromans; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Male; Metformin; Middle Aged; Thiazoles; Thiazolidinediones; Triglycerides; Troglitazone

To compare the long-term effects of the angiotensin-converting enzyme (ACE)-inhibitor quinapril and the cardioselective beta-adrenergic blocking agent metoprolol on glycaemic control, with glycosylated haemoglobin (HbA1c) as the principal variable, in non-insulin-dependent diabetes mellitus (NIDDM) patients with hypertension.. A randomized, double-blind, double-dummy, multicentre study during 6 months preceded by a 4 week wash-out and a 3 week run-in placebo period. Quinapril (20 mg) and metoprolol (100 mg, conventional tablets) were given once daily. No change was made in the treatment of diabetes (diet and hypoglycaemic agents).. Seventy-two patients fulfilling the criteria were randomized and entered the double-blind period. Twelve patients did not complete the study. Sixty patients, 26 on quinapril and 34 on metoprolol, were available for the final analysis.. The effect was assessed by changes in HbA1c, the fasting serum glucose and the post-load serum glucose, C-peptide and insulin levels during the oral glucose tolerance test.. In the quinapril group, the fasting serum glucose, oral glucose tolerance and the C-peptide and insulin responses, determined as the incremental area under the curves (AUC), showed no change, but the mean HbA1c level increased from 6.2 +/- 1.1% to 6.5 +/- 1.3% (P < 0.05). In the metoprolol group, the rise in the mean level of HbA1c, from 6.3 +/- 1.0% to 6.8 +/- 1.3% (P < 0.01), tended to be more marked than after quinapril, although there was no significant difference between the increments. The mean fasting serum glucose showed an increase from 9.1 +/- 1.9 mM to 10.1 +/- 2.8 mM (P < 0.01) which correlated significantly with the duration of diabetes (P < 0.01) and the increase in fasting serum triglycerides (P < 0.001). Moreover, in the metoprolol group we found significant decreases in the oral glucose tolerance as well as C-peptide and insulin responses to the glucose load.. Treatment with quinapril for 6 months appears to have advantages over metoprolol in NIDDM patients with hypertension. Although treatment with quinapril or metoprolol over 6 months was concomitant with a rise in the HbA1c, increased fasting blood glucose, decreased oral glucose tolerance and decreased C-peptide and insulin responses to a glucose challenge were observed only in patients treated with metoprolol.

Topics: Adrenergic beta-Antagonists; Aged; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Glucose; Blood Pressure; C-Peptide; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glucose Tolerance Test; Hemoglobin A; Humans; Hypertension; Insulin; Isoquinolines; Lipids; Male; Metoprolol; Middle Aged; Quality of Life; Quinapril; Sweden; Tetrahydroisoquinolines

The aim of this study was to compare the metabolic effects of a combination of daytime glibenclamide and evening NPH insulin with intensive insulin treatment (rapid acting insulin before meals and NPH insulin at bedtime) in patients exhibiting secondary failure to sulphonylurea treatment. Thirty-nine mildly obese NIDDM patients (BMI 25.6 +/- 0.5) were randomized after 6 weeks of intensive insulin treatment to either a combination treatment (CT, n = 20) or continued intensive insulin treatment (IT, n = 19). There were no differences between the two groups in age, diabetes duration, BMI, HbA1c, or basal and glucagon stimulated C-peptide. The patients were followed for 1 year and the findings were analysed on an intent to treat basis. Two patients in the CT group were excluded after 2 and 6 months, respectively, due to unacceptably high postprandial glucose values. There was a significant difference in HbA1c between the CT and IT groups at 6 months (8.2 +/- 0.2, n = 19, vs 6.8 +/- 0.4%, n = 19, p < 0.001)), but not at 12 months (7.8 +/- 0.3, n = 18, vs 7.5 +/- 0.4%, n = 19). After the initial intensive insulin treatment, BMI was constant in the CT group but increased significantly at 6 and 12 months in the IT group. We conclude that both treatments are associated with a marked and long-term improvement of glycaemic control. The intensive insulin treatment leads to a more pronounced weight increase which in the long run might have negative effect on overall metabolic control. Therefore, the combination treatment together with intensified education and dietary advice should be regarded as the initial treatment of choice for oral agent failure in moderately obese NIDDM patients.

Topics: Aged; Albuminuria; Analysis of Variance; Blood Glucose; Body Mass Index; C-Peptide; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glyburide; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin, Isophane; Insulin, Regular, Pork; Male; Metformin; Middle Aged; Sulfonylurea Compounds; Treatment Failure; Triglycerides

To examine whether intensive glycemic control could decrease the frequency or severity of diabetic microvascular complications, we performed a prospective study of Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM) treated with multiple insulin injection treatment. A total of 110 patients with NIDDM was randomly assigned to multiple insulin injection treatment group (MIT group) or to conventional insulin injection treatment group (CIT group). Fifty-five NIDDM patients who showed no retinopathy and urinary albumin excretions < 30 mg/24 h at the baseline were evaluated in the primary-prevention cohort, and the other 55 NIDDM patients who showed simple retinopathy and urinary albumin excretions < 300 mg/24 h were evaluated in the secondary-intervention cohort. The appearance and the progression of retinopathy, nephropathy and neuropathy were evaluated every 6 months over a 6-year period. The worsening of complications in this study was defined as an increase of 2 or more steps in the 19 stages of the modified ETDRS interim scale for retinopathy and an increase of one or more steps in 3 stages (normoalbuminuria, microalbuminuria and albuminuria) for nephropathy. The cumulative percentages of the development and the progression in retinopathy after 6 years were 7.7% for the MIT group and 32.0% for the CIT group in the primary-prevention cohort (P = 0.039), and 19.2% for MIT group and 44.0% for CIT group in the secondary-intervention cohort (P = 0.049). The cumulative percentages of the development and the progression in nephropathy after 6 years were 7.7% for the MIT group and 28.0% for the CIT group in the primary-prevention cohort (P = 0.032), and 11.5% and 32.0%, respectively, for the MIT and CIT groups in the secondary-intervention cohort (P = 0.044). In neurological tests after 6 years, MIT group showed significant improvement in the nerve conduction velocities, while the CIT group showed significant deterioration in the median nerve conduction velocities and vibration threshold. Although both postural hypotension and the coefficient of variation of R-R interval tended to improve in the MIT group, they deteriorated in the CIT group. In conclusion, intensive glycemic control by multiple insulin injection therapy can delay the onset and the progression of diabetic retinopathy, nephropathy and neuropathy in Japanese patients with NIDDM. From this study, the glycemic threshold to prevent the onset and the progression of diabetic microangio

Topics: Albuminuria; Blood Glucose; Blood Pressure; C-Peptide; Cholesterol; Cholesterol, HDL; Cohort Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Female; Humans; Insulin; Japan; Male; Middle Aged; Neural Conduction; Prospective Studies; Statistics, Nonparametric; Time Factors; Triglycerides

A total of 507, newly diagnosed, white Caucasian Type 2 diabetic patients entered into UK Prospective Diabetes Study, mean age 52 +/- 9 (SD) years have been compared with 195 age-matched normal subjects (fasting plasma glucose < 6 mmol l-1) who had no known first degree relatives with diabetes. Diabetic patients were more obese BMI(kg m-2) 30.1 +/- 6.2 vs 26.2 +/- 4.0, respectively, with female (F) diabetic patients more so than male (M). Fasting plasma glucose (mmol l-1) was 12.2 +/- 3.8 vs 5.0 +/- 0.6 in diabetic and normal subjects, and, haemoglobin A1c(%) 9.3 +/- 2.3 vs 5.4 +/- 0.4. Hyperinsulinaemia (mU l-1) was prevalent in both male and female diabetic patients, after adjustment for BMI (geometric mean 1SD interval, M 12.1 (11.8 to 12.4) vs 8.3(7.8 to 8.9) and F 13.3 (12.9 to 13.7) vs 7.4 (7.1 to 7.7). Plasma triglyceride (mmol l-1) was higher in diabetic patients, 1.8 (1.1 to 2.9) vs 1.1 (0.6 to 1.8). Total cholesterol (mmol-1) was slightly elevated in diabetic patients, with females in both populations higher than males, M 5.5 +/- 1.2 vs 5.2 +/- 0.9 and F 5.8 +/- 1.1 vs 5.5 +/- 1.1. HDL cholesterol (mmol l-1) was slightly lower in male and markedly lower in female diabetic patients than in normal subjects, M 1.00 +/- 0.26 vs 1.11 +/- 0.22 and F 1.12 +/- 0.27 vs 1.42 +/- 0.33. Urine albumin was raised in diabetic patients (mg l-1) 16.3 (5.2 to 50.9) vs 7.2 (3.2 to 16.5), as was urine N-acetylglucosaminidase (U l-1 6.4 (3.5 to 11.7) vs 2.9 (1.9 to 4.5) and plasma N-acetylglucosaminidase (U l-1) 11.5 +/- 3.2 vs 10.2 +/- 2.3. Normal subjects aged above 65 years, had slightly higher haemoglobin A1c, insulin, C-peptide, plasma and LDL cholesterol, triglyceride, plasma and urine N-acetylglucosaminidase and lower HDL cholesterol than younger subjects. The 2.5 and 97.5 percentiles for biochemical variables are presented for both populations aged 25-65 years.

Topics: Acetylglucosaminidase; Adult; Age Factors; Aged; Albuminuria; Biomarkers; Blood Glucose; C-Peptide; Cholesterol; Creatinine; Diabetes Mellitus, Type 2; Female; Fructosamine; Glycated Hemoglobin; Growth Hormone; Hexosamines; Humans; Hyperinsulinism; Insulin; Laboratories; Male; Middle Aged; Prevalence; Prospective Studies; Quality Control; Reference Values; Risk Factors; Sex Characteristics; Triglycerides; United Kingdom

The possible influence of C-peptide on renal function and metabolic control in patients with type 1 diabetes was examined in a double blind, randomized study. Nine patients received insulin and equimolar amounts of biosynthetic human C-peptide for 1 month (group 1), and nine were given insulin only (group 2). C-Peptide levels in plasma ranged from 0.3-2.6 nmol/L in group 1 during the study, whereas group 2 had undetectable levels. The urinary excretion of albumin in group 1 was 21 +/- 6 micrograms/min before the study and decreased by 40% and 55% after 2 and 4 weeks, respectively (P < 0.05). No change was seen in group 2. The glomerular filtration rate fell by 6% after 2 and 4 weeks (P < 0.05) in group 1, whereas no change was observed in group 2. Fluorescein leakage across the blood-retinal barrier decreased by 30% in group 1 (P < 0.05) and was unaltered in group 2. Hemoglobin-A1c and fructosamine values decreased by 9-16% in group 1 (P < 0.05), but not in group 2. The findings suggest that administration of C-peptide plus insulin, compared to insulin alone, to type 1 diabetic patients may reduce glomerular permeability and improve metabolic control.

Topics: Adolescent; Adult; Albuminuria; Blood Glucose; Blood-Retinal Barrier; C-Peptide; Diabetes Mellitus, Type 1; Double-Blind Method; Female; Fluorescein; Fluoresceins; Fructosamine; Glomerular Filtration Rate; Glucagon; Glycated Hemoglobin; Growth Hormone; Hexosamines; Humans; Insulin; Insulin Infusion Systems; Kidney; Male; Norepinephrine; Pilot Projects

To investigate the effects of metformin on glycemic control, insulin resistance, and risk factors for cardiovascular disease in NIDDM subjects from two ethnic groups (Caucasian and Asian) with different risks of cardiovascular disease.. A total of 27 subjects with NIDDM (17 Caucasian, 10 Asian) were given metformin and placebo each for a 12-wk period in a randomized, double-blind, placebo-controlled crossover study, and the dose was increased after 1 and 6 wk, up to a maximum of 850 mg three times a day. Insulin resistance, glycemic control, and cardiovascular risk factors were assessed before and after each treatment phase. The end of 12 wk of metformin treatment was compared with the end of 12 wk of placebo treatment.. Metformin treatment was associated with significant improvement in FPG at 6 and 12 wk (mean difference at 12 wk, -3.08 mM, 95% CI -4.12 to -2.04 mM, P < 0.0001) and MCR of glucose (median difference 0.40 ml.kg-1.min-1, interquartile range -0.10 to 1.30 ml.kg-1.min-1, P = 0.036). beta-cell function calculated by HOMA also improved significantly (median difference 14%, interquartile range 7 to 23%, P < 0.001). Total triglyceride (median difference -0.2 mM, interquartile range -0.6 to 0.1 mM, P = 0.034), total cholesterol (mean difference -0.52 mM, 95% CI -0.83 to -0.22 mM, P = 0.002), and LDL cholesterol (mean difference -0.40 mM, 95% CI -0.64 to -0.16 mM, P = 0.002) fell significantly on metformin treatment, whereas no significant changes were observed in HDL cholesterol. PAI-1 activity fell significantly (mean difference -5.3 AU/ml, 95% CI -8.2 to -2.4 AU/ml, P = 0.001), but plasma fibrinogen concentrations and platelet function, spontaneous or agonist induced, were unaffected. UAE was lower on metformin treatment (median difference -2.4 micrograms/min, interquartile range -4.4 to -0.2 micrograms/min, P = 0.004), but metformin had no significant effect on BP. The effects of metformin on glycemic control and cardiovascular risk factors were generally similar in the two ethnic groups.. These findings indicate that metformin treatment improves glycemic control, and lowers insulin resistance and risk factors for cardiovascular disease, including PAI-1, and may therefore be useful in the long-term management of NIDDM subjects who have a high risk of cardiovascular disease.

Topics: Albuminuria; Asia; Biomarkers; Blood Glucose; C-Peptide; Cardiovascular Diseases; Cholesterol; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Double-Blind Method; Ethnicity; Fructosamine; Hexosamines; Humans; Insulin; Insulin Resistance; Islets of Langerhans; Metabolic Clearance Rate; Metformin; Plasminogen Activator Inhibitor 1; Platelet Aggregation; Risk Factors; Triglycerides; United Kingdom; White People

The effect of a blood pressure reduction by 10 mg extended release felodipine once daily on urinary albumin excretion (UAE) as well as the possible diabetogenic effect of felodipine was studied. A 2 X 12 week placebo-controlled double-blind crossover study was performed in 12 hypertensive non-insulin-dependent diabetic (NIDDM) patients without nephropathy on concomitant treatment with beta-blocker and/or a diuretic agent. Metabolic control as estimated by fasting plasma glucose, hemoglobin A1c and fasting plasma C-peptide was unaltered after felodipine. Blood pressure was significantly reduced by felodipine: systolic 166 +/- 26 mm Hg (placebo) v 153 +/- 26 mm Hg (felodipine) (P less than .05) and diastolic 95 +/- 7 mm Hg v 90 +/- 8 mm Hg (P less than .05). Heart rate was unchanged. There was no correlation between blood pressure and UAE, but the relative change in UAE expressed as UAE placebo/UAE felodipine was significantly correlated to the fall in systolic blood pressure (r = 0.64, P = .03) and mean blood pressure (r = 0.66, P = .02). Since microalbuminuria predicts proteinuria and reduced survival, early antihypertensive treatment may be beneficial in NIDDM as it is in IDDM. Long-term consequences on kidney function and mortality remains, however, to be elucidated.

Topics: Aged; Albuminuria; Blood Pressure; C-Peptide; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Double-Blind Method; Fasting; Felodipine; Female; Glycated Hemoglobin; Heart Rate; Humans; Hypertension; Male; Middle Aged

To explore the association between retinal neurodegeneration and metabolic parameters in progressive dysglycemia.. A cross-sectional study was performed on 68 participants: normal glucose tolerance (n = 23), prediabetes (n = 25), and Type 2 diabetes without diabetic retinopathy (n = 20). Anthropometric assessment and laboratory sampling for HbA1c, fasting glucose, insulin, c-peptide, lipid profile, renal function, and albumin-to-creatinine ratio were conducted. Central and pericentral macular thicknesses on spectral domain optical coherence tomography were compared with systemic parameters.. Baseline demographic characteristics were similar across all groups. Cuzick's trend test revealed progressive full-thickness macular thinning with increasing dysglycemia across all three groups (P = 0.015). The urinary albumin-to-creatinine ratio was significantly correlated with full-thickness superior (R = -0.435; P = 0.0002), inferior (R = -0.409; P = 0.0005), temporal (R = -0.429; P = 0.003), and nasal (R = -0.493; P < 0.0001) pericentral macular thinning, after post hoc Bonferroni adjustment. There was no association between macular thinning and waist circumference, body mass index, blood pressure, lipid profile, or insulin resistance.. Progressive dysglycemia is associated with macular thinning before the onset of visible retinopathy and occurs alongside microalbuminuria. Retinal neurodegenerative changes may help identify those most at risk from dysglycemic end-organ damage.

Topics: Aged; Albuminuria; Blood Glucose; C-Peptide; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Glucose Metabolism Disorders; Glycated Hemoglobin; Humans; Insulin; Lipids; Male; Middle Aged; Prediabetic State; Retinal Degeneration; Tomography, Optical Coherence

Cardiovascular and renal complications are the predominant causes of morbidity and mortality amongst patients with diabetes. Development of novel treatments have been hampered by the lack of available animal models recapitulating the human disease. We hypothesized that experimental diabetes in rats combined with a cardiac or renal stressor, would mimic diabetic cardiomyopathy and nephropathy, respectively. Diabetes was surgically induced in male Sprague Dawley rats by 90% pancreatectomy (Px). Isoprenaline (Iso, 1 mg/kg, sc., 10 days) was administered 5 weeks after Px with the aim of inducing cardiomyopathy, and cardiac function and remodeling was assessed by echocardiography 10 weeks after surgery. Left ventricular (LV) fibrosis was quantified by Picro Sirius Red and gene expression analysis. Nephropathy was induced by Px combined with uninephrectomy (Px-UNx). Kidney function was assessed by measurement of glomerular filtration rate (GFR) and urine albumin excretion, and kidney injury was evaluated by histopathology and gene expression analysis. Px resulted in stable hyperglycemia, hypoinsulinemia, decreased C-peptide, and increased glycated hemoglobin (HbA1c) compared with sham-operated controls. Moreover, Px increased heart and LV weights and dimensions and caused a shift from α-myosin heavy chain (MHC) to β-MHC gene expression. Isoprenaline treatment, but not Px, decreased ejection fraction and induced LV fibrosis. There was no apparent interaction between Px and Iso treatment. The superimposition of Px and UNx increased GFR, indicating hyperfiltration. Compared with sham-operated controls, Px-UNx induced albuminuria and increased urine markers of kidney injury, including neutrophil gelatinase-associated lipocalin (NGAL) and podocalyxin, concomitant with upregulated renal gene expression of NGAL and kidney injury molecule 1 (KIM-1). Whereas Px and isoprenaline separately produced clinical endpoints related to diabetic cardiomyopathy, the combination of the two did not accentuate disease development. Conversely, Px in combination with UNx resulted in several clinical hallmarks of diabetic nephropathy indicative of early disease development.

Topics: Albuminuria; Animals; C-Peptide; Diabetes Mellitus, Experimental; Diabetic Cardiomyopathies; Diabetic Nephropathies; Disease Models, Animal; Fibrosis; Glomerular Filtration Rate; Heart; Isoproterenol; Kidney; Lipocalin-2; Male; Pancreatectomy; Rats; Rats, Sprague-Dawley; Renal Insufficiency

The aim was to determine if persistent c-peptide in long duration childhood onset (<17 years) type 1 diabetes (T1D) related to microvascular complications.. Pittsburgh Epidemiology of Diabetes Complications (EDC) participants (n = 185) had serum c-peptide levels measured by Mercodia ultra-sensitive ELISA at the 25-year follow-up exam. Microvascular complications between those with and without detectable c-peptide were compared.. Eighteen (9.7%) participants had detectable median c-peptide levels of 3.8 (2.6, 12.2) pmol/L and did not differ from those without detectable levels. No differences in microalbuminuria, confirmed distal symmetric polyneuropathy, renal failure, or between those with one or more complications were found between the two groups. Proliferative retinopathy (PR) was marginally lower in those with detectable c-peptide (33.3% vs 55.1%, p = 0.08). However, those with c-peptide were somewhat less likely to have fasted for a full 8-h (66.7% vs. 84.9%, p = 0.09). Excluding those not fully fasted, PR no longer approached significance but macroalbuminuria became marginally lower in those with detectable levels (23.4% vs 0%, p = 0.07).. Low levels of c-peptide in T1D patients of long duration were detected but were not strongly related to microvascular complications.

Topics: Adolescent; Adult; Albuminuria; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Neuropathies; Diabetic Retinopathy; Female; Glycated Hemoglobin; Humans; Male; Risk Factors; Time Factors; Young Adult

We previously showed the deleterious effects of increased dietary protein on renal manifestations and glucose metabolism in leptin receptor-deficient (db) mice. Here, we further examined its effects on glucose metabolism, including urinary C-peptide. We also orally administered mixtures corresponding to low- or high-protein diets to diabetic mice.. In diet experiments, under pair-feeding (equivalent energy and fat) conditions using a metabolic cage, mice were fed diets with different protein content (L diet: 12 % protein, 71 % carbohydrate, 17 % fat; H diet: 24 % protein, 59 % carbohydrate, 17 % fat) for 15 days. In oral administration experiments, the respective mixtures (L mixture: 12 % proline, 71 % maltose or starch, 17 % linoleic acid; H mixture: 24 % proline, 59 % maltose or starch, 17 % linoleic acid) were supplied to mice. Biochemical parameters related to glucose metabolism were measured.. The db-H diet mice showed significantly higher water intake, urinary volume, and glucose levels than db-L diet mice but similar levels of excreted urinary C-peptide. In contrast, control-H diet mice showed significantly higher C-peptide excretion than control-L diet mice. Both types of mice fed H diet excreted high levels of urinary albumin. When maltose mixtures were administered, db-L mixture mice showed significantly higher blood glucose after 30 min than db-H mixture mice. However, db mice administered starch-H mixture showed significantly higher blood glucose 120-300 min post-administration than db-L mixture mice, although both groups exhibited similar insulin levels.. High-protein, low-carbohydrate diets deteriorated diabetic conditions and were associated with insufficient insulin secretion in db mice. Our findings may have implications for dietary management of diabetic symptoms in human patients.

Topics: Albuminuria; Animals; Blood Glucose; Body Weight; C-Peptide; Carbohydrate Metabolism; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, Carbohydrate-Restricted; Dietary Carbohydrates; Dietary Proteins; Insulin; Insulin Secretion; Leptin; Male; Maltose; Mice; Mice, Inbred C57BL; Mice, Knockout; Starch

We previously demonstrated that polymorphisms in the carnosinase-1 gene (CNDP1) determine the risk of nephropathy in type 2 diabetic patients. Carnosine, the substrate of the enzyme encoded by this gene, is considered renoprotective and could possibly be used to treat diabetic nephropathy (DN). In this study, we examined the effect of carnosine treatment in vivo in BTBR (Black and Tan, BRachyuric) ob/ob mice, a type 2 diabetes model which develops a phenotype that closely resembles advanced human DN. Treatment of BTBR ob/ob mice with 4 mM carnosine for 18 weeks reduced plasma glucose and HbA1c, concomitant with elevated insulin and C-peptide levels. Also, albuminuria and kidney weights were reduced in carnosine-treated mice, which showed less glomerular hypertrophy due to a decrease in the surface area of Bowman's capsule and space. Carnosine treatment restored the glomerular ultrastructure without affecting podocyte number, resulted in a modified molecular composition of the expanded mesangial matrix and led to the formation of carnosine-acrolein adducts. Our results demonstrate that treatment with carnosine improves glucose metabolism, albuminuria and pathology in BTBR ob/ob mice. Hence, carnosine could be a novel therapeutic strategy to treat patients with DN and/or be used to prevent DN in patients with diabetes.

Topics: Administration, Oral; Albuminuria; Animals; Blood Glucose; C-Peptide; Carnosine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dipeptidases; Disease Models, Animal; Gene Expression; Glomerular Mesangium; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Kidney Glomerulus; Male; Mice; Mice, Obese; Organ Size

Type 1 diabetes mellitus (T1DM) is characterized by the deficiencies of insulin and C-peptide. Mounting evidences have proved the beneficial effects of C-peptide on the renal function in T1DM. However, it is still controversial about the roles of C-peptide in T2DM nephropathy since the level of C-peptide fluctuates greatly at different stages of T2DM. In the present study, we found that the serum C-peptide concentration was much lower in GK rats with diabetic nephropathy than that in normal counterparts. A sustained supplementation of C-peptide at a physiological level could ameliorate urinary albumin, independent of blood glucose control. C-peptide treatment improved glomerulosclerosis and podocyte morphology and reduced the thickness of glomerular basement membrane as compared with saline treatment control. Moreover, it decreased fibronectin synthesis in diabetic glomeruli and in cultured rat mesangial cells accompanied by a down-regulation of RAGE and an up-regulation of PKA. Interestingly, H-89, a PKA inhibitor, could reverse the inhibition effect of C-peptide on fibronectin production in cultured mesangial cells. These findings suggest that C-peptide level is low in T2DM rats with nephropathy and a treatment with a physiological dose of C-peptide can prevent renal injury in diabetic GK rats.

Topics: Albuminuria; Animals; C-Peptide; Cyclic AMP-Dependent Protein Kinases; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Enzyme Activation; Fibronectins; Kidney; Male; Rats; Receptor for Advanced Glycation End Products; Receptors, Immunologic

Vitamin D deficiency has been related to diabetes, hypertension, hyperlipidemia and peripheral vascular disease. In this study, we aimed to investigate the role of vitamin D status in non-alcoholic fatty liver disease.. We included 211 consecutive subjects to examine the presence of non-alcoholic fatty liver disease. Of these subjects, 57 did not have non-alcoholic fatty liver disease and 154 had non-alcoholic fatty liver disease.. The non-alcoholic fatty liver disease group had significantly higher fasting blood glucose (p = 0.005), uric acid (p = 0.001), aspartate aminotransferase (p<0.001), alanine aminotransferase (p<0.001), γ-glutamyltransferase (p<0.0001), alkaline phosphatase (p = 0.028), HbA1c (p<0.001), ferritin (p<0.001), insulin (p = 0.016), C-peptide (p = 0.001), HOMA-IR (p = 0.003), total cholesterol (p = 0.001), triglyceride (p = 0.001) and white blood cell (p = 0.04) levels. In contrast, the non-alcoholic fatty liver disease group had significantly lower 25(OH)D levels (12.3±8.9 ng/dl, p<0.001) compared with those of the control group (20±13.6 ng/dl).. In this study, we found lower serum 25(OH)D levels in patients with non-alcoholic fatty liver disease than in subjects without non-alcoholic fatty liver disease. To establish causality between vitamin D and non-alcoholic fatty liver disease, further interventional studies with a long-term follow-up are needed.

Topics: Adult; Albuminuria; Blood Glucose; C-Peptide; Creatinine; Fasting; Female; Humans; Insulin; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Outpatients; Regression Analysis; Seasons; Vitamin D; Vitamin D Deficiency

This study describes the clinical characteristics of childhood- and adolescent-onset type 2 diabetes mellitus (CAT2DM) seen at a diabetes center in southern India.. Between January 1992 and December 2009, 368 CAT2DM patients were registered. Anthropometric measurements were done using standardized techniques. Biochemical investigations included C-peptide measurements and glutamic acid decarboxylase antibody assay wherever feasible. Retinopathy was diagnosed by retinal photography; microalbuminuria, if urinary albumin excretion was between 30 and 299 mg/μg of creatinine; nephropathy, if urinary albumin excretion was ≥300 mg/μg; and neuropathy, if vibration perception threshold on biothesiometry was ≥20 V.. The proportion of CAT2DM patients, expressed as percentage of total patients registered at our center, rose from 0.01% in 1992 to 0.35% in 2009 (P<0.001). Among the 368 cases of CAT2DM, 96 (26%) were diagnosed before the age of 15 years. The mean age at first visit and age at diagnosis of the CAT2DM subjects were 22.2±9.7 and 16.1±2.5 years, respectively. Using World Health Organization growth reference charts, 56% of boys and 50.4% of girls were >85(th) percentile of body mass index for age. Prevalence rates of retinopathy, microalbuminuria, nephropathy, and neuropathy were 26.7%, 14.7%, 8.4%, and 14.2%, respectively. Regression analysis revealed female gender, body mass index >85(th) percentile, parental history of diabetes, serum cholesterol, and blood pressure to be associated with earlier age at onset of CAT2DM.. CAT2DM appears to be increasing in urban India, and the prevalence of microvascular complications is high. Female predominance is seen at younger ages.

Topics: Adolescent; Age Distribution; Age of Onset; Albuminuria; Analysis of Variance; Blood Pressure; Body Mass Index; C-Peptide; Child; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Female; Humans; India; Male; Prevalence; Risk Assessment; Risk Factors; Sex Distribution; Young Adult

Previous studies have demonstrated that renoprotective effects of C-peptide in experimental models of diabetes-induced renal disease may be mediated via lowering blood glucose. The present study examined the renoprotective effects of C-peptide in a model of nondiabetic renal disease, the Dahl salt-sensitive (SS/jr) rat. SS/jr rats were placed on a 2% NaCl diet for 2 wk (HS2, resulting in mild to moderate renal injury) or 4 wk (HS4, resulting in advanced renal injury) and then received either vehicle (veh) or C-peptide (Cpep) for additional 4 wk. Urine albumin (UAE) and protein (UPE) excretion rates were measured at baseline (i.e., before initiation of veh or Cpep treatment) and 4 wk later (i.e., at the time of death). Glomerular permeability, indexes of glomerulosclerosis and tubulointerstitial fibrosis, the presence of inflammatory cells, and protein expression of transforming growth factor-β (TGF-β) and podocin were measured at the time of death. In HS2 + veh rats, UAE and UPE increased by 74 and 92%, respectively, from baseline and the time of death. While HS2 + Cpep attenuated this increase in UAE and UPE, HS4 + Cpep had no effect on these parameters. Similarly, HS2 + Cpep reduced glomerular permeability, tubulointerstitial fibrosis, renal inflammation, TGF-β, and podocin protein expression, while HS4 + Cpep had no effect. These studies indicate that C-peptide is renoprotective in nondiabetic experimental models with mild to moderate renal injury.

Topics: Albuminuria; Animals; C-Peptide; Fibrosis; Glomerulosclerosis, Focal Segmental; Intracellular Signaling Peptides and Proteins; Kidney Glomerulus; Male; Membrane Proteins; Nephritis, Interstitial; Permeability; Rats; Rats, Inbred Dahl; Sodium Chloride, Dietary; Transforming Growth Factor beta

Type 2 diabetes mellitus and obstructive sleep apnea syndrome (OSAS) are serious comorbidities. Effects of OSAS on diabetic microvascular complications are ongoing research subjects. We evaluated the incidence of OSAS in Type 2 diabetes mellitus patients with nephropathy and with no renal involvement.. A total of 52 people with diabetes were enrolled in this study. Patients body mass indices were calculated and fasting glucose, glycosylated hemoglobin, urea, creatinine, total lipid profile, and urinary albumin excretion were evaluated. Full polysomnography was used to detect sleep disorders.. Baseline characteristics and laboratory results of the patients were similar. Meeting criteria for OSAS was detected in 35 of the 54 patients (67.3%). 25 patients (48%) had mild, six patients (11.5%) had moderate, and four patients (7.7%) had severe sleep disorders. There was no significant relationship between respiratory obstructive parameters and microalbuminuria (R=0.91, p=0.362). Substantial correlation was detected between lower values of serum triglyceride levels and lower respiratory indices (R=0.299, p=0.031).. In type 2 diabetes accompanying OSAS affects glucose regulation but its effect on nephropathy development is currently a subject of research.

Topics: Albuminuria; Biomarkers; Blood Glucose; Body Mass Index; C-Peptide; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Glycated Hemoglobin; Humans; Lipids; Male; Middle Aged; Polysomnography; Prospective Studies; Sleep Apnea, Obstructive; Turkey

Several intervention studies have convincingly demonstrated the importance of good glycemic control to avoid long-term diabetic complications, but the importance of other risk factors remains controversial. We previously reported a markedly reduced incidence of severe retinopathy and nephropathy during the past decades in an unselected population of type 1 diabetes mellitus diagnosed in childhood. The aim of the present study was to analyze possible risk factors, which could explain the improved prognosis.. In this longitudinal population-based cohort study, we followed all 269 patients in whom type 1 diabetes mellitus was diagnosed in childhood 1961-1985 in a well-defined geographical area in Sweden. The patients were followed until the end of 1990 s. Multivariable regression models were used to analyze the importance of hemoglobin A1c (HbA(1c)), diabetes duration, blood pressure, cardiovascular risk factors and persisting C-peptide secretion for the development of diabetic retinopathy and nephropathy.. Beside longer duration and higher HbA(1c), blood pressure and lipid values were higher and cardiovascular disease and smoking were more common in patients with severe complications. However, multivariable analysis abolished these associations. Diabetes duration and long-term HbA(1c) were the only significant independent risk factors for both retinopathy and nephropathy. The risk of overt nephropathy increased substantially when HbA(1c) was above 9.6% [Diabetes Control and Complications Trial (DCCT) corrected value], while the risk of severe retinopathy increased already when HbA(1c) exceeded 8.6%.. In this unselected population, glycemic control was the only significant risk factor for the development of long-term complications.

Topics: Age of Onset; Albuminuria; Blood Glucose; Blood Pressure; Body Mass Index; C-Peptide; Cardiovascular Diseases; Child; Cholesterol; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Retinopathy; Glycated Hemoglobin; Homeostasis; Humans; Triglycerides

Topics: Adult; Albuminuria; C-Peptide; Diabetes Mellitus, Type 1; Female; Humans; Intercellular Adhesion Molecule-1; Interleukin-18; Male; Vascular Cell Adhesion Molecule-1

Derangements of the GH-IGF-I axis have been associated with microalbuminuria (MA) in type 1 diabetes. The aim of this study was to investigate whether an IGF-I gene promoter polymorphism influenced the development of persistent MA in type 1 diabetes.. A prospective follow-up study of a cohort of 277 patients with newly diagnosed type 1 diabetes consecutively enrolled between September 1979 and August 1984.. Urinary albumin excretion rate over 24 h was measured in each patient at least once a year. Persistent MA was defined as a urinary albumin excretion rate between 30 and 300 mg/24 h.. During a median follow-up of 18.0 years (range 1.0-21.5), 79 of 277 patients developed persistent MA. IGF-I gene genotype was available for 216 subjects; in 73% of the subjects, the wild-type genotype of this IGF-I gene polymorphism was present, while 27% had the variant type. At baseline, there were no differences in IGF-I levels and HbA(1c) values between subjects with the wild type and subjects with variant type. By Kaplan-Meier analysis, subjects with the variant type of this polymorphism had during follow-up a higher risk of development of MA compared subjects with the wild type (P = 0.03).. Subjects with the variant type of an IGF-I gene polymorphism had a significantly increased risk of developing MA. This risk was not mediated through changes in circulating IGF-I levels. Our study suggests that in type 1 diabetes, this IGF-I gene polymorphism is a risk factor of MA.

Topics: Adolescent; Adult; Albuminuria; Alleles; Blood Pressure; C-Peptide; Child; Child, Preschool; Diabetes Complications; Diabetes Mellitus, Type 1; DNA; Female; Gene Frequency; Genotype; Humans; Infant; Insulin-Like Growth Factor I; Male; Polymorphism, Genetic; Promoter Regions, Genetic; Risk

The present study investigated the relationship between hemoglobin (Hb) levels and autonomic failure using a sensitive marker, coefficient of variation of R-R intervals in electrocardiogram (CVR-R) in order to clarify a cause of normocytic normochromic anemia in type 1 diabetic patients without overt nephropathy. We recruited 46 patients with type 1 diabetes and measured creatinine clearance (Ccr), HbA1c, albuminuria, Hb levels and CVR-R of all patients. In addition, the status of diabetic retinopathy and neuropathy were also evaluated. Serum erythropoietin (EPO), Fe, total iron binding capacity, lactate dehydrogenase, total bilirubin levels and number of reticulocytes and mean corpuscular volume were also measured to distinguish types of anemia. To survey the statistical correlation existing between Hb and body mass index (BMI), Ccr, HbA1c, albuminuria or retinopathy, multiple regression analysis was performed. Serum EPO, Fe, TIBC, LDH and TB levels and number of reticulocytes and MCV were within normal limits. Multiple regression analysis disclosed that HbA1c, nephropathy evaluated by albuminuria and Ccr, and retinopathy has no concern with Hb level. There is only significant relationship between Hb levels and CVR-R. Similar results were obtained even if we analyzed a group of male and female separately. We conclude that CVR-R has the strong relationship on anemia without overt nephropathy in type 1 diabetes, indicating that autonomic failure contributes on the progression of anemia via a poor response of EPO to anemia.

Topics: Adult; Aged; Albuminuria; Anemia; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Electrocardiography; Erythropoietin; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Sensitivity and Specificity

The objective of the study was to analyse levels IL-12 and to relate the findings to the clinical course of type 1 diabetes mellitus (DM1).. We examined a group of 102 children with DM1 and 39 healthy children (as the control). All the children with DM1 had their daily urine albumin excretion, HbA1c, C-peptide measured, 24hrs blood pressure monitoring and ophthalmologic examination. In accordance to the ophthalmologic examination and level IL-12 in the serum the diabetic children were divided into 3 groups: group A: IL-12>0 pg/ml; group B: IL-12=0 pg/ml; group C: IL-12=0 pg/ml and IL12>0 pg/ml. Serum levels of IL-12 and TNFalpha were measured by the immunoenzymatic ELISA method, Quan-tikine High Sensitivity Human by R&D Systems (USA).. Children of group A were characterized by significantly high level of IL-12 and by the absence of TNFalpha as compared with the children of group B, who had undetectable IL-12 along with high TNFalpha level. Additionally, children of group A had significantly lower urine albumin excretion and had only developed retinopathy. However, the children of group B not only had retinopathy, nephropathy but also arterial hypertension. The patients of group A were also analysed against the children of group C, who were characterized by high IL-12 level and some of them had also detectable TNFalpha, but without retinopathy and nephropathy.. The results of our study imply the existence of balance between IL-12 and TNFalpha in type 1 DM children, which seems to warrant the stage of disease without diabetic complications. However, the IL-12 domination tends to prevent or delay nephropathy development but does not protect from retinopathy.

Topics: Adolescent; Albuminuria; Angiogenesis Inducing Agents; Angiogenesis Inhibitors; Biomarkers; C-Peptide; Child; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Diabetic Retinopathy; Female; Glycated Hemoglobin; Humans; Hypertension; Interleukin-12; Male; Neovascularization, Pathologic; Reference Values; Tumor Necrosis Factor-alpha

Despite that numerous investigations on the nature of diabetic microangiopathy were carried out, its pathomechanism remains unclear.. The aim of the study was to analyze the relation between early diabetic microangiopathy and the proinflammatory cytokines, NAG and its A and B isoforms in blood and urine in children diagnosed with diabetes mellitus type 1.. The study was carried out on the group of 56 children with diabetes mellitus 1 (age 13.6+/-3.74) and 35 healthy children selected as the controls. All the patients had 24 hrs albuminuria, HbA1c, C-peptide as well as the NAG enzyme and its A and B isoforms serum and urine activities measured. Additionally, all the children had TNF-a and IL6 level in serum measured. Each patient had 24 hrs blood pressure monitored and underwent ophthalmologic examination.. Children with long-standing diabetes mellitus and retinopathy (group 1, n=15) were older and were characterized by a statistically significant longer duration of the disease and higher HbA1c level in comparison with the patients who presented with no sign of diabetic retinopathy (group 2, n=41). In the group 1 statistically significant higher TNF-alpha serum level (p=0.01), NAG (p=0.002) and its isoforms A (p=0.007) and B (p=0.001) urine activities were measured in relation to the group 2. Additionally the level of IL-6 and NAG and its isoforms A and B serum activities were higher in group 1 than in group 2, however the differences were of no statistical significance. Moreover the children from group 2 in comparison with the healthy controls showed statistically significant higher TNF-alpha serum activity (p=0.016) and NAG (p<0.001) and its A (p<0.001) and B (p<0.001) isoforms both serum and urine activities.. The occurrence of the detectable serum TNF-alpha activity in children with diabetes mellitus type 1 showing no sign of diabetic retinopathy and nephropathy and no microalbuminuria with the concomitant increase of NAG and its isoforms serum and urine activities might point toward prompt occurrence of these changes in the eye and the kidneys.

Topics: Adolescent; Albuminuria; Biomarkers; C-Peptide; Child; Comorbidity; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Diabetic Retinopathy; Female; Glycated Hemoglobin; Human Development; Humans; Hypertension; Interleukin-6; Male; Protein C; Risk Factors; Tumor Necrosis Factor-alpha

There is accumulating evidence that C-peptide exerts beneficial renal effects in type-1 diabetes by reducing glomerular hyperfiltration, albuminuria and glomerular hypertrophy in the early stage of nephropathy. The aim of this study was to clarify further the effects of C-peptide on renal structural changes in type-1 diabetic rats.. The effects of C-peptide or placebo on glomerular volume, mesangial expansion, glomerular basement membrane thickness, albuminuria and glomerular filtration rate (GFR) were studied in three groups of rats: a non-diabetic group (N, n=9) and two groups that, during 8 weeks of diabetes, were left untreated for 4 weeks and then given a subcutaneous infusion of either placebo (D, n=11) or C-peptide (DCp, n=11) during the next 4 weeks. Furthermore, GFR was studied after 4 weeks of diabetes in an additional diabetic group (D-early, n=9) and in an age-matched non-diabetic group (N-early, n=9).. After 4 weeks, GFR in the D-early group was 102% higher than in the N-early group. GFR after 8 weeks did not differ between the study groups. The D group presented with a 33% larger glomerular volume than the N group (P<0.001), while glomerular volume in the DCp group was similar to that in the N-group. Total mesangial and mesangial matrix fractions were increased by 46% (P<0.001) and 133% (P<0.001), respectively, in the D group. The corresponding values in the DCp group did not differ from those for the non-diabetic animals. Neither the thickness of the glomerular basement membrane nor the level of albuminuria differed significantly between the study groups.. C-peptide administration in replacement dose to streptozotocin-diabetic rats serves to limit or prevent the glomerular hypertrophy and the mesangial matrix expansion seen in the post-hyperfiltration phase of early diabetic nephropathy.

Topics: Albuminuria; Animals; Basement Membrane; C-Peptide; Diabetes Mellitus, Experimental; Glomerular Filtration Rate; Glomerular Mesangium; Kidney Glomerulus; Male; Organ Size; Rats; Rats, Wistar; Streptozocin

to assess the relations among plasma levels of von Willebrand factor (vWf), microalbuminuria and markers of oxidative stress in patients with type 2 diabetes mellitus.. We studied 10 healthy subjects without microalbuminuria or history of coronary artery disease (CAD) and 30 patients with type 2 diabetes mellitus who were classified into three groups, each including 10 patients of matched age and sex; group 1: patients without microalbuminuria or history of CAD; group 2: patients with microalbuminuria and no history of CAD, and group 3: patients with microalbuminuria and history of CAD. All subjects underwent laboratory measurements of vWf, albumin excretion rate (AER), malondialdehyde, vitamin C, reduced glutathione and C peptide.. vWf was elevated in patients with type 2 diabetes mellitus compared with control subjects. However, levels were higher in patients with than without microalbuminuria and in patients with than without a history of CAD (96+/-12, 124+/-7, 149+/-9, 175+/-7 in the control subjects and the diabetic patients' groups respectively). There was a positive correlation between vWf and AER, MDA and C- peptide (r=0.91, 0.98, 0.96, p<0.0001) and a negative correlation between vWf and both vitamin C and reduced glutathione (r=-0.59 and -0.62 respectively, p<0.001).. vWf levels are elevated in patients with type 2 diabetes mellitus, particularly in the presence of microalbuminuria and history of CAD. vWf levels are associated with markers of increased oxidative stress and therefore reflect the severity of biochemical abnormalities, which contribute to diabetic vascular disease.

Topics: Albuminuria; Ascorbic Acid; C-Peptide; Diabetes Mellitus, Type 2; Female; Glutathione; Humans; Male; Malondialdehyde; Oxidative Stress; Platelet Adhesiveness; von Willebrand Factor

To determine the prevalence and factors associated with diabetic retinopathy in the Australian population and to estimate the time difference between disease onset and clinical diagnosis of type 2 diabetes.. The Australian Diabetes, Obesity and Lifestyle study (AusDiab) included 11,247 adults aged > or =25 years in 42 randomly selected areas of Australia. Retinopathy was assessed in participants identified as having diabetes (based on self-report and oral glucose tolerance test), impaired fasting glucose, and impaired glucose tolerance and in a random sample with normal glucose tolerance. Data were available for 2,177 participants.. Overall, 15.3% of those with diabetes had retinopathy. The prevalence of retinopathy was 21.9% in those with known type 2 diabetes (KDM) and 6.2% in those newly diagnosed (NDM). The prevalence of proliferative diabetic retinopathy (PDR) was 2.1% in those with KDM. No cases of PDR were found in those with NDM. Untreated vision threatening retinopathy (presence of PDR or macular edema) was present in 1.2% (n = 4). Factors associated with retinopathy were duration of diabetes, HbA(1c), and systolic blood pressure. Using linear extrapolation of the prevalence of retinopathy with diabetes duration, the onset of diabetes in this population was approximately the time of diagnosis.. This is one of the first national studies of diabetic retinopathy in a developed country. The prevalence of retinopathy was similar to that in other population-based studies. Vision threatening retinopathy was relatively rare; however, four untreated cases were identified. Regular screening for diabetic retinopathy and more aggressive management of modifiable risk factors could reduce the numbers of people who develop vision-threatening retinopathy.

Topics: Age of Onset; Aged; Albuminuria; Australia; Blood Glucose; Blood Pressure; C-Peptide; Diabetes Mellitus; Diabetic Retinopathy; Female; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Lipids; Male; Middle Aged; Prevalence; Risk Factors; Smoking

This study examined the metabolic effects of heart transplantation in patients in end-stage cardiac failure.. A total of 18 patients after heart transplantation for end-stage heart disease (age 47 +/- 3 years; transplant age 5.5 +/- 1.5 years; BMI 25.8 +/- 0.8 kg/m(2); cyclosporin A 4.2 +/- 0.6 mg/[kg.day]; azathioprine 0.87 +/- 0.31 mg/[kg.day]), 12 patients with type 2 diabetes (D-Tx), and 6 patients without type 2 diabetes (Tx) were studied by means of 1) an oral glucose tolerance test (OGTT) to assess the beta-cell secretory response, 2) a euglycemic-hyperinsulinemic (1 mU/[kg.min]) clamp combined with indirect calorimetry and a primed continuous infusion of [6,6-2H2]glucose and [1-13C]leucine to measure postabsorptive and insulin-stimulated carbohydrate and protein metabolism, and 3) 1H-NMR spectroscopy of the calf muscles to measure intramyocellular triglyceride (IMCL) content. The patients were selected from 480 transplant patients in whom there was a 6% prevalence of type 2 diabetes. Five healthy subjects matched for anthropometric parameters served as control subjects (CON).. Tx had postabsorptive and insulin-stimulated glucose, leucine, and free fatty acid metabolism, as well as IMCL content, similar to that of CON. D-Tx were characterized by a reduced secretory response during the OGTT and peripheral insulin resistance with respect to glucose metabolism, which was paralleled by increased plasma free fatty acid concentrations and IMCL content. A defective insulin-dependent suppression of the endogenous leucine flux (index of proteolysis) was also evident during the clamp in D-Tx.. Heart transplantation, notwithstanding the immunosuppressive therapy, was characterized by a normal postabsorptive and insulin-stimulated glucose, leucine, and free fatty acid metabolism in Tx. In contrast, insulin resistance with respect to glucose, free fatty acids, and protein metabolism was present in D-Tx regardless of whether diabetes was preexisting or consequent to heart transplantation.

Topics: Adult; Albuminuria; Blood Glucose; C-Peptide; Cholesterol; Diabetes Mellitus; Diabetic Neuropathies; Energy Metabolism; Female; Follow-Up Studies; Glucagon; Glucose Clamp Technique; Heart Transplantation; Humans; Insulin; Lipids; Male; Middle Aged; Neural Conduction

Abnormalities of glucose metabolism and hyperinsulinemia have been demonstrated in patients with end-stage renal disease and may contribute to the development of atherosclerotic complications in these patients. In the present study, we investigated the stage of renal failure in which abnormalities of glucose metabolism develop and whether these abnormalities were associated with an increased prevalence of cardiovascular events in patients with early renal failure. In 321 untreated essential hypertensive patients, we assessed renal function by measuring 24-h creatinine clearance, urinary protein excretion, and microalbuminuria; we assessed cardiovascular status by clinical and laboratory tests; and we measured plasma glucose, insulin, and C-peptide levels at fasting and after a 75-g oral glucose load. To evaluate insulin sensitivity, a hyperinsulinemic-euglycemic clamp was performed in a subgroup of 104 patients. Patients with creatinine clearance < 30 ml.min(-1).1.73 m(-2), severe hypertension, BMI < 30 kg/m(2), and diabetes or family history of diabetes were excluded. Hypertensive patients were found to be hyperinsulinemic when compared with 92 matched normotensive subjects. Early renal failure (creatinine clearance < 90 ml.min(-1).1.73 m(-2)) caused by hypertensive nephrosclerosis was detected in 116 of 321 patients. Analysis of patients with varying degrees of renal function impairment demonstrated increased plasma glucose and insulin response to oral glucose load, decreased fasting glucose-to-insulin ratio, and reduced sensitivity to insulin only in those patients with creatinine clearance < 50 ml.min(-1).1.73 m(-2). Parameters of glucose metabolism were not correlated with creatinine clearance and microalbuminuria. Prevalence of atherosclerotic cardiovascular events was significantly related to reduction of creatinine clearance, but parameters of glucose metabolism were comparable in patients with and without evidence of atherosclerotic damage. Thus, in patients with hypertensive nephrosclerosis and early impairment of glomerular filtration, alterations of glucose metabolism become evident only when creatinine clearance is < 50 ml.min(-1).1.73 m(-2) and are not related to microalbuminuria and cardiovascular complications.

Topics: Albuminuria; Blood Glucose; Body Mass Index; C-Peptide; Creatinine; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Humans; Hyperinsulinism; Hypertension; Insulin; Kidney Failure, Chronic; Male; Middle Aged; Proteinuria; Reference Values; Smoking; Triglycerides

The urinary excretion of insulinotropic glucagon-like peptide 1 (GLP-1) was investigated as an indicator of renal tubular integrity in 10 healthy subjects and in 3 groups of type 2 diabetic patients with different degrees of urinary albumin excretion rate. No significant difference emerged between the groups with respect to age of the patients, known duration of diabetes, metabolic control, BMI, or residual beta-cell pancreatic function. Endogenous creatinine clearance was significantly reduced under conditions of overt diabetic nephropathy, compared with normo and microalbuminuric patients (p < 0.01). Urinary excretion of GLP-1 was significantly higher in normoalbuminuric patients compared to controls (490.4 +/- 211.5 vs. 275.5 +/- 132.1 pg/min; p < 0.05), with further increase under incipient diabetic nephropathy conditions (648.6 +/- 305 pg/min; p < 0.01). No significant difference resulted, in contrast, between macroproteinuric patients and non-diabetic subjects. Taking all patients examined into account, a significant positive relationship emerged between urinary GLP-1 and creatinine clearance (p = 0.004). In conclusion, an early tubular impairment in type 2 diabetes would occur before the onset of glomerular permeability alterations. The tubular dysfunction seems to evolve with the development of persistent microalbuminuria. Finally, the advanced tubular involvement, in terms of urinary GLP1 excretion, under overt diabetic nephropathy conditions would be masked by severe concomitant glomerular damage with the coexistence of both alterations resulting in a peptide excretion similar to control subjects.

Topics: Aged; Albuminuria; Body Mass Index; C-Peptide; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Glycated Hemoglobin; Humans; Male; Metabolic Clearance Rate; Middle Aged; Peptide Fragments

Strict glycemic control and antihypertensive treatment may decrease but not eliminate the risk of progressive nephropathy in diabetic patients. C-peptide has been shown to exert beneficial effects on complications, including incipient nephropathy, in type 1 diabetes.. Renal effects of 14 days of intravenous infusion of C-peptide or NaCl (placebo) were studied in three groups of rats: one nondiabetic NaCl-treated (normal, N = 7), one streptozotocin diabetic NaCl-treated (D-placebo, N = 7), and one streptozotocin diabetic C-peptide-treated group (D-C-p, N = 7). Metabolic data and albuminuria were measured in metabolic cages every fourth day. After 14 days, the glomerular filtration rate (GFR) was measured by inulin clearance and available renal functional reserve (RFR) by glycine infusion, whereupon one kidney was perfusion fixed for morphological studies.. Glucose levels were 36.7 +/- 1.3 and 34.0 +/- 1.7 mmol/L in the D-placebo and D-C-p groups, respectively. The D-placebo group presented a 32% (P < 0.001) larger glomerular volume than the D-C-p group. The D-placebo group also presented a significantly larger renal weight than the normal group in contrast to the D-C-p group. Urinary albumin excretion increased in the D-placebo group in contrast to the other groups. GFR was 1.72 +/- 0.12 mL/min (normal), 3.73 +/- 0.19 mL/min (D-placebo, P < 0.001 vs. normal) and 2.16 +/- 0.16 mL/min (D-C-p, nonsignificant vs. normal). Available RFR was 93 +/- 25% (normal), 10 +/- 4% (D-placebo, P < 0.05 vs. normal) and 57 +/- 13% (D-C-p, nonsignificant vs. normal) of basal GFR.. Physiological doses of homologous C-peptide prevent the development of glomerular hypertrophy, albuminuria, and glomerular hyperfiltration in rats with experimentally induced diabetes.

Topics: Albuminuria; Animals; C-Peptide; Diabetes Mellitus, Experimental; Glomerular Filtration Rate; Kidney; Kidney Glomerulus; Male; Organ Size; Rats; Rats, Sprague-Dawley

To determine the influence of residual beta-cell function on retinopathy and microalbuminuria we measured basal C-peptide in 50 type 1 diabetic outpatients aged 24.96 +/- 7.14 years, with a duration of diabetes of 9.1 +/- 6.2 years. Forty-three patients (86%) with low C-peptide (<0.74 ng/ml) had longer duration of diabetes than 7 patients (14%) with high C-peptide (> or =0.74 ng/ml) (9 (2-34) vs 3 (1-10) years, P = 0.01) and a tendency to high glycated hemoglobin (HBA1) (8.8 (6-17.9) vs 7.7 (6.9-8.7)%, P = 0. 08). Nine patients (18%) had microalbuminuria (two out of three overnight urine samples with an albumin excretion rate (AER) > or =20 and <200 microg/min) and 13 (26%) had background retinopathy. No association was found between low C-peptide, microalbuminuria and retinopathy and no difference in basal C-peptide was observed between microalbuminuric and normoalbuminuric patients (0.4 +/- 0.5 vs 0.19 +/- 0.22 ng/ml, P = 0.61) and between patients with or without retinopathy (0.4 +/- 0.6 vs 0.2 +/- 0.3 ng/ml, P = 0.43). Multiple regression analysis showed that duration of diabetes (r = 0. 30, r2 = 0.09, P = 0.031) followed by HBA1 (r = 0.41, r2 = 0.17, P = 0.01) influenced basal C-peptide, and this duration of diabetes was the only variable affecting AER (r = 0.40, r2 = 0.16, P = 0.004). In our sample of type 1 diabetic patients residual ss-cell function was not associated with microalbuminuria or retinopathy.

Topics: Adult; Albumins; Albuminuria; Analysis of Variance; C-Peptide; Creatinine; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Humans; Islets of Langerhans; Male

Our aim was to compare the diurnal blood pressure patterns of people with Type 1 diabetes on continuous ambulatory peritoneal dialysis (CAPD, n=9) or haemodialysis (n=10) to diabetic patients with normo-albuminuria (n=12) or micro-albuminuria (n=15). Blood pressure was measured with an ABPM02 Meditech oscillometric blood pressure monitor. The micro-albuminuric group had significantly higher nocturnal diastolic and mean arterial pressures than the normo-albuminuric group. CAPD and haemodialysis patients had significantly higher day time, nocturnal mean systolic, diastolic and mean arterial blood pressures. Micro-albuminuric and end-stage renal failure patients displayed a loss of the physiological drop of systolic blood pressure, which was only significant in the normo-albuminuric group. Nocturnal drop of blood pressure characterised by diurnal indices were 7.4% in the CAPD, 8.8% in the haemodialysis, 10.0% in the micro-albuminuric and 16.5% in the normo-albuminuric group. These results suggest, that pathological circadian blood pressure variation is common in diabetic patients on dialysis, and ambulatory blood pressure monitoring can be a useful tool both in its the detection and its adequate treatment.

Topics: Adult; Albuminuria; beta 2-Microglobulin; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Blood Urea Nitrogen; C-Peptide; Cholesterol; Circadian Rhythm; Creatinine; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Glycated Hemoglobin; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis; Triglycerides

Syndrome X is used to describe a constellation of factors that lead to coronary heart disease (CHD): hypertension, hyperinsulinemia, impaired glucose tolerance, and an abnormality in lipid metabolism. We investigated the relationship between serum levels of C-peptide immunoreactivity (CPR) and diabetic complications in 256 patients with type-2 diabetes mellitus. The serum level of CPR was measured by radioimmunoassay (RIA). Diabetic patients were divided into 3 groups according to the serum level of CPR as follows: low CPR (n = 19, <0.7 ng/ml), normal CPR (n = 174, 0.7 to 2.2 ng/ml) and high CPR (n = 63, >2.2 ng/ml). The body mass index (BMI) and the serum level of triglycerides were significantly higher in the high CPR group (P < 0.05, respectively) compared with normal CPR group. The prevalence of hypertension was significantly higher in the high CPR group than in the other 2 groups (low CPR: 16%, normal CPR: 28%, high CPR: 38%). The frequency of the number of patients receiving insulin therapy was greater in the low CPR group than in the other 2 groups, (low CPR: 58%, normal CPR: 15%, high CPR: 11%). The serum CPR level was significantly lower in patients with than without proliferative retinopathy or macroalbuminuria. Our conclusion is that the present data suggest that an increased serum level of CPR is associated with obesity, elevated serum triglycerides, and hypertension in patients with type-2 diabetes mellitus. A low CPR level leading to hyperglycemia is associated with the progression of diabetic microangiopathies, such as retinopathy and nephropathy.

Topics: Albuminuria; Body Mass Index; C-Peptide; Coronary Disease; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Retinopathy; Female; Humans; Hypertension; Hypertriglyceridemia; Insulin; Male; Middle Aged; Obesity; Risk Factors

Preperitoneal fat is an indicator of visceral fat deposition, which is closely related to atherosclerosis and coronary heart disease in obese patients. We assessed the relationship of preperitoneal fat deposition and various clinical characteristics in 90 patients with non-insulin-dependent diabetes mellitus (NIDDM). Preperitoneal and subcutaneous fat deposition were measured by ultrasonography. In both the male and female diabetics, preperitoneal fat levels were significantly higher than in age-matched healthy subjects. We also determined blood pressures, fasting plasma glucose, glycosylated hemoglobin A1c, serum lipids, fasting immunoreactive insulin (FIRI), daily urinary C-peptide (CPR), serum leptin, urinary albumin excretion and body mass index (BMI). Of these parameters, BMI, FIRI, leptin and daily urinary CPR were positively correlated with preperitoneal fat deposition. Patients with diet therapy alone showed significantly higher preperitoneal fat levels than those receiving insulin therapy. In female, patients with increased preperitoneal fat showed higher prevalence of hypertension than those with decreased fat. Macroalbuminuric patients had a lower preperitoneal fat than microalbuminuric and normoalbuminuric patients. Patients with proliferative retinopathy exhibited lower preperitoneal fat than did those without retinopathy. Preperitoneal fat levels were positively correlated with motor or sensory nerve conduction velocity.. The present findings suggest that in NIDDM patients, increased preperitoneal fat deposition is closely associated with obesity, hypertension and hyperinsulinemia, and negatively modulates diabetic microangiopathy including nephropathy, retinopathy and neuropathy.

Topics: Adipose Tissue; Albuminuria; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Fasting; Female; Humans; Hypoglycemic Agents; Insulin; Leptin; Male; Middle Aged; Neural Conduction; Peritoneum; Proteins; Reference Values; Sensation; Skin; Time Factors; Ultrasonography

Topics: Adipose Tissue; Age Factors; Age of Onset; Aged; Albuminuria; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Retinopathy; Female; Hemoglobin A; Humans; Male; Middle Aged

Topics: Albuminuria; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Food; Humans

The correlation between hypertension and related risk factors has been studied in 733 type 2 diabetic patients. Hypertension was more frequent in women (65.35%) than in men (50.35%) (p < 0.0001).. Hypertensive patients showed older age (p < 0.0001) and greater Body Mass Index (BMI) (p < 0.03) than normotensive. In the diabetic group on diet only basal insulinaemia was higher (p < 0.05) in hypertensive than in normotensive diabetic men, but not in women. Such a difference, was not seen in patients of both sexes treated with oral hypoglycaemic agents; besides there was no difference in fasting C-peptide levels between hypertensive and normotensive insulin treated patients. In both sexes hypertension was independently correlated with age, BMI, increased urinary albumin excretion, triglycerides. The strongest correlation was with the family history of hypertension. On the contrary there was no correlation between hypertension and waisthip ratio.. In conclusion, the association between hypertension and type 2 diabetes depends on various risk factors, but a relationship with insulin levels is not surely demonstrable.

Topics: Administration, Oral; Adult; Age Factors; Aged; Albuminuria; Blood Glucose; Body Constitution; Body Mass Index; C-Peptide; Comorbidity; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Genetic Predisposition to Disease; Humans; Hypercholesterolemia; Hyperinsulinism; Hypertension; Hypertriglyceridemia; Hypoglycemic Agents; Insulin; Insulin Resistance; Italy; Male; Middle Aged; Obesity; Prevalence; Risk Factors

The aim of this study was to determine whether renal functional reserve (RFR) is altered in insulin-dependent diabetic (IDDM) patients according to the stage of diabetic nephropathy. RFR was examined in 33 IDDM patients in similar glycaemic and metabolic control and compared to 12 healthy control subjects, during eight 1 h clearance periods prior to, during and after a 3-h stimulation by amino acid infusion (4.5 mg x kg(-1) x min[-1]). RFR was calculated as the difference between stimulated and baseline glomerular filtration rates (GFR). In 14 early normotensive diabetic patients with normal urinary albumin excretion, mean baseline GFR (133 +/- 3 ml x min(-1) x 1.73 m[-2]) was higher whereas RFR (10 +/- 4 ml x min(-1) x 1.73 m[-2]) was lower (p < 0.05) than in control subjects (113 +/- 4 and 28 +/- 2 ml x min(-1) x 1.73 m(-2), respectively). In 10 normotensive patients who had lived with IDDM for 16 years and who had microalbuminuria, baseline GFR and RFR (109 +/- 7 and 24 +/- 6 ml x min(-1) x 1.73 m(-2), respectively) were similar to those in control subjects. In 9 patients who had suffered IDDM for 23 years and had developed macroalbuminuria and hypertension, baseline GFR (78 +/- 8 ml x min(-1) x 1.73 m[-2]) was lower than in control subjects (p < 0.05) and RFR (8 +/- 4 ml x min(-1) x 1.73 m[-2]) was not significant. In addition, renal vascular resistance decreased significantly during infusion (p < 0.05) in microalbuminuric normotensive patients as well as in control subjects (by 9 +/- 4 and 11 +/- 4 mmHg x l(-1) x min(-1) x 1.73 m(-2), respectively) but not in normoalbuminuric normotensive or macroalbuminuric hypertensive patients. These results indicate that microalbuminuric normotensive patients retain a normal RFR, whereas RFR is reduced or suppressed at two opposite stages of the disease: in normoalbuminuric normotensive patients with a high GFR and in macroalbuminuric hypertensive patients with a decreased GFR. This dissimilar impairment reveals permanent glomerular hyperfiltration in both early IDDM without nephropathy and IDDM with overt diabetic nephropathy, but not in IDDM with incipient nephropathy.

Topics: Adult; Albuminuria; Aldosterone; Amino Acids; Blood Glucose; Blood Pressure; C-Peptide; Creatinine; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Nephropathies; Dietary Proteins; Female; Glomerular Filtration Rate; Glycated Hemoglobin; Humans; Hypertension; Kidney; Male; Reference Values; Renal Circulation; Renin; Vascular Resistance

C-peptide is co-secreted with insulin and has generally been considered not to possess biological activity. However, several recent studies during the last five years have demonstrated that administration of C-peptide in physiological amounts to type 1 diabetes (IDDM) patients on a short term basis (1-3h) results in decreased glomerular hyperfiltration, augmented glucose utilization and improved autonomic nerve function. More prolonged administration (1-3 months) of C-peptide to IDDM patients is accompanied by improvements in both renal function (diminished microalbuminuria) and autonomic and sensory nerve function. Both in vitro and in vivo data indicate that C-peptide may have a role in the regulation of insulin secretion. C-peptide's mechanism of action is not known but it may be related to its ability to stimulate Na+, K(+)-ATPase, activity, probably by activating a receptor coupled to a pertussis toxin-sensitive G-protein with subsequent activation of Ca2(+)-dependent intracellular signaling pathways. In conclusion, the combined findings indicate that C-peptide is a biologically active hormone. The possibility that C-peptide therapy in IDDM patients may be beneficial should be considered.

Topics: Albuminuria; Amino Acid Sequence; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Enzyme Activation; Heart Rate; Insulin; Insulin Secretion; Kidney; Molecular Sequence Data; Peptide Fragments; Sodium-Potassium-Exchanging ATPase

Topics: Albuminuria; Black or African American; Black People; Blood Glucose; Blood Pressure; C-Peptide; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Humans; Male; Prevalence; Time Factors; Urban Health

Topics: Albuminuria; Bilirubin; Blood Glucose; Blood Proteins; C-Peptide; Cyclosporine; Diabetes Mellitus, Type 2; Fibrosis; Glucocorticoids; Humans; Hypoglycemic Agents; Immunosuppressive Agents; Insulin; Liver Transplantation; Male; Middle Aged; Nutritional Status; Prednisone; Radioimmunoassay; Triglycerides; Uric Acid

The prevention of diabetic nephropathy is as yet an unresolved issue. The aim of our study was to assess the effects of transplantation of long-term cultured and cryopreserved fetal pancreas islets on metabolic control and the development of diabetic nephropathy.. Serum C-peptide, glucose, HbA1c, insulin requirements, urinary albumin excretion rate, and blood pressure of 10 insulin-dependent diabetic patients after transplantation were compared with a group of 27 insulin-dependent diabetic controls on insulin therapy only during a 10-year follow-up.. In the first year after transplantation mean insulin requirement decreased from 53.6+/-2.2 to 35.8+/-1.2 units. C-peptide levels appeared (0.55+/-0.08 ng/ml) and remained detectable throughout the follow-up. Blood glucose and HbA1c were significantly (P<0.05) lower than in the controls. Mean albumin excretion rates of the transplant and the control groups during the follow up were 18.8+/-8.5 and 11.7+/-2.0, 16.6+/-6.6 and 14.0+/-2.3, 15.0+/-5.0 and 15.1+/-2.7, 15.3+/-7.5 and 20.4+/-4.2, 19.8+/-6.2 and 36.7+/-11.1, 11.7+/-3.6 and 51.3+/-14.6, 14.1+/-4.2 and 71.4+/-23.1, 22.7+/-8.6 and 92.0+/-28.1, 18.0+/-5.9 and 107.6+/-35.6, 21.7+/-11.0 and 101.5+/-29.3 microg/min respectively. From the 6th year the difference between the two groups was significant (P<0.001). In the transplant group initial mean systolic and diastolic blood pressure values were 132.0+/-3.3 and 81.5+/-1.5 mmHg, in the controls 130.4+/-3.4 and 79.6+/-1.6 mmHg respectively. Significant changes (P<0.05) of blood pressure during the follow-up or differences between the two groups were not observed.. We conclude that fetal islet transplantation is effective in achieving good long-term diabetes control and in the prevention of diabetic nephropathy.

Topics: Adult; Albuminuria; C-Peptide; Female; Fetal Tissue Transplantation; Follow-Up Studies; Glycated Hemoglobin; Humans; Islets of Langerhans Transplantation; Male

To clarify whether beta-cell function deteriorates with increasing albuminuria and duration of diabetes, we investigated the insulin and c-peptide response to oral glucose tolerance test in 47 healthy subjects and 75 normoalbuminuric (group 1), 30 microalbuminuric (group 2), and 35 macroalbuminuric (group 3) Type 2 diabetes mellitus patients. The total area under the insulin curve (AUCI) values of groups 1, 2, and 3 were 245 +/- 16, 193 +/- 17, and 88 +/- 8 pmol/L.h, respectively, significantly lower than that (624 +/- 34 pmol/L.h) of the healthy group. The mean total area under the c-peptide curve (AUCC-P) values of groups 1, 2, and 3, respectively, were 2.50 +/- 0.11, 2.05 +/- 0.15, and 1.73 +/- 0.07 nmol/L.h, respectively, significantly lower than that (5.47 +/- 0.19 nmol/L.h) of the healthy controls. The mean AUCI and AUCC-P values of group 3 were significantly reduced compared to those of group 1. The mean AUCI and AUCC-P values of patients with 0-5, 5-10, 10-15, and > 15 years' duration were significantly decreased compared to those of healthy subjects. The mean AUCI and AUCC-P values of patients with > 15 years' duration were significantly lower than those of patients with 0-5 years' duration. The mean hemoglobin Alc values of the three diabetic groups were not significantly different. These data suggest that beta-cell function deterioration was associated with increasing albuminuria and diabetic duration in Type 2 diabetic patients.

Topics: Albuminuria; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Humans; Insulin; Islets of Langerhans; Male; Middle Aged; Time Factors

Increasing attention is being paid to disturbances in glucose metabolism as key explanatory factors for the development of coronary artery disease. We studied the prevalence of impaired glucose tolerance and non-insulin-dependent diabetes and the levels of plasma insulin after an oral glucose tolerance test in 99 men with heart disease but without a history of diabetes referred to coronary arteriography; we also compared the outcome with a matched control group (n = 116). The severity of atherosclerosis in coronary angiograms was evaluated according to glucose tolerance status. Among the 99 patients with coronary artery disease, 37.4% had an abnormal oral glucose tolerance test result, whereas only 18.1% of the control group had an abnormal result (p < 0.01). Moreover, patients with heart disease and normal glucose tolerance were hyperinsulinemic compared with the control group (p < 0.01). By analysis of variance no statistically significant difference in severity of coronary atherosclerosis on coronary angiograms was found. In conclusion, we demonstrated frequent disturbances in glucose metabolism indicating insulin resistance in patients with ischemic heart disease without a history of diabetes, but we could not demonstrate a relation between these disturbances and degree of coronary atherosclerosis.

Topics: Adult; Aged; Albuminuria; Analysis of Variance; Blood Glucose; C-Peptide; Case-Control Studies; Coronary Angiography; Coronary Artery Disease; Coronary Disease; Diabetes Mellitus, Type 1; Glucose; Glucose Tolerance Test; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Male; Middle Aged; Myocardial Ischemia; Prevalence; Proinsulin

To evaluate the prevalence in obese patients of an increased urinary albumin excretion rate (UAER) and the factors involved in this parameter.. Two hundred and seven nondiabetic obese patients with BMI = 34.7 +/- 5.7 (SD) kg/m2. None had proteinuria or a history of nephropathy or uropathy. Fifty-two had moderate hypertension. A control group of 22 lean healthy subjects was also studied.. The UAER was determined from 24-h urine samples by means of immunonephelemetry laser method. Creatinine clearance was calculated. Glycemia and plasma C peptide at fasting and 120 mine after glucose oral administration, HbA1c, serum fructosamine, plasma total cholesterol and triglycerides, HDL and LDL cholesterol were measured. Food intakes were determined by dietary history.. Compared with the control group, the UAER was significantly higher in the obese patients (18.0 +/- 20.1 mg/24 h vs 3.2 +/- 2.8 mg/24 h, P < 0.0001). It was elevated (> 30 mg/24 h) in 25 obese patients (12.1%) and in particular, in 19.2% of the obese patients with hypertension. It was significantly higher in the patients with android or mixed (both android and gynoid) obesity than in those with gynoid obesity (p = 0.050). Log UAER correlated negatively with the duration of hypertension (p = 0.038) and was higher in the patients with familial hypertension than in those without (p = 0.002). Log UAER correlated strongly with log creatinine clearance (p < 0.0001) and fractional albumin clearance (p < 0.0001). It correlated significantly with fasting and 120 min after glucose plasma C peptide concentrations (p = 0.018 and p = 0.046, respectively). Creatinine clearance was significantly higher in the patients with android or mixed obesity than in those with gynoid obesity (p = 0.001). Log creatinine clearance correlated negatively with age (p = 0.046), and log LDL cholesterol (p = 0.025) and positively with log lipid caloric intake (p = 0.014).. These results show the high prevalence of microalbuminuria in nondiabetic obese patients and suggest the involvement of renal hyperfiltration. Microalbuminuria may be an indicator of familial hypertension in obese subjects. Insulin resistance may be involved in the increase in the UAER. Nutritional factors, particularly lipid intake, may contribute to this increase in the UAER via an increase in glomerular hyperfiltration.

Topics: Adult; Albuminuria; Blood Pressure; C-Peptide; Cholesterol; Creatinine; Female; Fructosamine; Glomerular Filtration Rate; Glucose Tolerance Test; Glycated Hemoglobin; Hexosamines; Humans; Hypertension; Linear Models; Male; Middle Aged; Obesity; Prevalence; Time Factors; Triglycerides

To investigate whether insulin resistance and microalbuminuria are associated in non-insulin-dependent diabetes mellitus (NIDDM).. Insulin sensitivity was assessed using a hyperinsulinemic euglycemic clamp in 11 normoalbuminuric and 9 microalbuminuric NIDDM patients matched for sex, age, body composition, glycemic control, diabetes duration, and therapy.. Isotopically determined glucose disposal was similar in normo- and microalbuminuric patients in the basal state (mean +/- SD; 3.30 +/- 1.01 vs. 3.46 +/- 0.82 mg.kg lean body mass [LBM]-1.min-1; NS) and during hyperinsulinemia (7.16 +/- 2.65 vs. 6.63 +/- 2.88 mg.kg LBM-1.min-1;NS). No difference was observed in nonoxidative glucose disposal or lipid oxidation. Endogenous glucose production was equally suppressed by insulin (-0.08 +/- 0.99 vs. 0.30 +/- 1.12 mg.kg-1 LBM.min-1; NS). Glucose oxidation tended to be lower in the normoalbuminuric patients in the basal state (1.16 +/- 0.37 vs. 1.41 +/- 0.36 mg.kg LBM-1.min-1) and during hyperinsulinemia (2.35 +/- 0.72 vs. 2.90 +/- 0.77 mg.kg LBM-1.min-1; both P < 0.15). Urinary albumin excretion rate correlated with the insulin-stimulated glucose oxidation rate (r = 0.59, P = 0.0064), and a similar trend was seen in the basal state (r = 0.42, P = 0.063). Protein oxidation was higher in normoalbuminuric patients (1.6 +/- 0.5 vs. 1.0 +/- 0.4 mg.kg LBM-1.min-1; P = 0.017) and correlated inversely with albuminuria (r = -0.70, P = 0.0007). Serum growth hormone increased during insulin infusion; however, the increase was significantly greater in microalbuminuric patients. Plasma lipoproteins, maximal aerobic capacity, and 24-h ambulatory blood pressure were similar in the two groups.. Basal and insulin-stimulated glucose uptakes are comparable in carefully matched normo- and microalbuminuric NIDDM patients, and glucose oxidation may be positively related to albuminuria. The inverse relation between protein oxidation and albuminuria may be due to higher growth hormone levels during daily life perturbations in glucose in microalbuminuric patients.

Topics: Albuminuria; Blood Glucose; Body Composition; C-Peptide; Calorimetry; Circadian Rhythm; Diabetes Mellitus, Type 2; Diastole; Female; Fructosamine; Glucose; Glucose Clamp Technique; Glycated Hemoglobin; Glycolysis; Heart Rate; Hexosamines; Humans; Infusions, Intravenous; Insulin; Insulin Resistance; Male; Middle Aged; Oxidation-Reduction; Reference Values; Regression Analysis; Systole; Tritium

To address the relationship of insulin-like growth factor-I (IGF-I) to diabetes control, we determined IGF-I levels in 137 subjects age 17 yr and younger with recently diagnosed insulin-dependent diabetes mellitus in a population-based cohort study between 3 and 11 months after diagnosis (mean 4.9 months). Initial determinations of IGF-I, 24-h urine C-peptide and microalbuminuria, age, sex, height, weight, body mass index, pubertal stage, and glycosylated hemoglobin (GHb) were obtained. IGF-I levels ranged from 11-439 ng/mL, were strongly related to age (r = 0.74, P < 0.001), and were higher in females than males at any given age (P < 0.01). IGF-I was inversely related to GHb (partial r = -0.43, P < 0.001) after adjustment for sex and age. The relationship between IGF-I and GHb did not change between age groups (< 6, 6-9, > or = 10 yr of age; P = 0.50), and it did not change between prepubertal and pubertal subjects (P = 0.95). IGF-I was not related to 24-h urine C-peptide or microalbuminuria. These results suggest that lower IGF-I levels are related to poorer metabolic control of diabetes in the period following insulin-dependent diabetes mellitus diagnosis in all young persons regardless of age or pubertal status.

Topics: Adolescent; Age Factors; Albuminuria; Blood Glucose; Body Mass Index; C-Peptide; Child; Cohort Studies; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Insulin-Like Growth Factor I; Male; Puberty; Radioimmunoassay; Sex Characteristics; Sex Factors; Time Factors

We have evaluated the feasibility of monitoring the 24-hour urinary excretion rate of C-peptide (U-CPR) as a measure of integrated beta-cell function in patients with non-insulin-dependent diabetes mellitus (NIDDM). In 37 normoalbuminuric patients, U-CPR of 117.9 +/- 9.1 micrograms/d (mean +/- SEM) during the poorly controlled glycemic phase (fasting plasma glucose [FPG], 171 +/- 7 mg/dL; hemoglobin A1C [HbA1c], 8.8% +/- 0.4%) was significantly higher than the value of 83.3 +/- 13.7 micrograms/d (P < .001) during the well-controlled phase (FPG, 135 +/- 6 mg/dL; HbA1c, 7.0% +/- 0.2%), although the plasma insulin response to meals was lower during the former phase (53.3 +/- 6.3 microU/mL) versus the latter phase (65.7 +/- 6.6, P < .005). Endogenous creatinine clearance (Ccr) was significantly elevated during the poorly controlled phase (105.4 +/- 7.3 v 88.7 +/- 4.7 mL/min, P < .005). In 26 microalbuminuric patients, the plasma insulin response was greater during good glycemic control, but U-CPR did not differ between the two phases. Ccr was comparable at two phases in this group (92.7 +/- 7.4 v 91.1 +/- 5.9 mL/min, NS). U-CPR correlated positively with Ccr in both groups (r = .593, P < .001 in normoalbuminuria; r = .585, P < .001 in microalbuminuria). In addition, when biosynthetic human C-peptide was infused intravenously at an identical rate in two healthy subjects, resulting steady-state plasma levels of CPR were lower, and fractional U-CPR was higher during the moderately hyperglycemic phase versus the euglycemic phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Albuminuria; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Glomerular Filtration Rate; Glycated Hemoglobin; Humans; Hyperglycemia; Male; Metabolic Clearance Rate; Middle Aged

To assess the long-term relationships between 24-h ambulatory blood pressure (AMBP), urinary albumin excretion (UAE) rate, and metabolic control in non-insulin-dependent diabetes mellitus (NIDDM) patients with normo- and microalbuminuria.. We conducted a prospective study of 23 NIDDM patients (11 with normoalbuminuria and 12 with microalbuminuria) receiving standard clinical care, including antihypertensive treatment, attending the outpatient clinic and 8 healthy control subjects. Twenty-four-hour AMBP and UAE were measured synchronously in addition to fasting plasma glucose, HbA1c, and serum creatinine at baseline and after 4.6 (4.2-5.1) years [mean (range)].. Baseline systolic, but not diastolic, 24-h AMBP was significantly higher in diabetic patients compared with control subjects (146/80 [16/11] vs. 133/78 [9/9] mmHg, P < 0.05), but was similar in normoalbuminuric (143/81 [11/11] mmHg) and microalbuminuric (148/80 [20/10] mmHg) patients during strict blood pressure control. The annual increase in 24-h AMBP was equivalent in diabetic patients (0.6/-0.2 [2.6/1.5] mmHg/year) and control subjects (0.7/0.2 [1.2/1.4] mmHg/year, NS) and not significantly different from zero. Overall UAE did not change in control subjects (5.6 [1.6] vs. 4.4 [1.9]) (geometric mean [antilog SD]) or in the normoalbuminuric (8.7 [1.7] vs. 11.3 [3.0] micrograms/min) and microalbuminuric (35.7 [2.1] vs. 34.5 [3.2] micrograms/min) patients. In diabetic patients, the annual change in UAE correlated significantly with the annual change in the systolic (r = 0.61, P < 0.002) and diastolic (r = 0.54, P < 0.008) 24-h AMBP. In microalbuminuric patients, only the annual increase in systolic 24-h AMBP correlated significantly with the annual change in UAE (r = 0.71, P = 0.010), whereas in the normoalbuminuric patients, only the annual increase in diastolic 24-h AMBP and the annual change in UAE were significantly correlated (r = 0.66, P = 0.026). In a stepwise multiple linear regression analysis, the annual progression in albuminuria in NIDDM patients was significantly determined by increases in systolic (parameter estimate 0.018, SE 0.006, P < 0.008) as well as in diastolic 24-h AMBP (parameter estimate 0.026, SE 0.011, P < 0.033).. In an outpatient clinical setting, 24-h AMBP is similar in NIDDM patients with normo- and microalbuminuria. Alterations in both 24-h AMBP and UAE are on average moderate and equivalent compared with those in healthy control subjects. Although the average change in albuminuria is small, a progression in albuminuria relates to increments in both systolic and diastolic 24-h AMBP.

Topics: Albuminuria; Analysis of Variance; Antihypertensive Agents; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; C-Peptide; Case-Control Studies; Cholesterol; Cholesterol, HDL; Circadian Rhythm; Confidence Intervals; Diabetes Mellitus, Type 2; Diastole; Female; Glycated Hemoglobin; Humans; Hypertension; Male; Middle Aged; Prospective Studies; Reference Values; Regression Analysis; Systole; Triglycerides

The aim of this work was to evaluate the prevalence of microalbuminuria in an obese population and to study the relation between albumin excretion rate (AER), various clinical (body mass index, adipose tissue distribution) nutritional (macronutrient intake) and metabolic parameters. A cross-sectional study was carried out, and AER was evaluated in 182 obese subjects (BMI > 27) with no medication, no intercurrent disease, no cardiac, pulmonary or endocrinological disorders (including diabetes and hypertension) and also in 31 control subjects at the outpatient clinic of the department of Nutrition, Hôtel Dieu, Paris, France. The following were measured: BMI, waist/hip ratio (WHR), urinary AER, blood glucose, insulin and C peptide levels, cholesterol (CT), triglycerides, HDL cholesterol (HDL-CT), apoprotein A1 and B. In the obese population, 18 subjects (9.9%) were found to have an increased AER: 13 subjects (7.1%) with microalbuminuria (AER between 30 to 300 mg/24 h) and five with AER over 300 mg/24 h. AER was normal in all control subjects but one, who was found to have microalbuminuria. Log AER was positively correlated to WHR (P < 0.001), blood pressure (P < 0.05), cholesterol (P < 0.05), Apo B levels (P < 0.01) and with fasting Insulin levels and protein intake (P < 0.001). Positive association between log AER and protein intake, insulin levels, Apo B and blood pressure were found independently of BMI and WHR. It is suggested that abdominal obesity may be associated with incipient nephropathy in some obese subjects without diabetes and hypertension. Microalbuminuria may be included among metabolic abnormalities connected with abdominal-type excess weight distribution.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adipose Tissue; Adult; Albuminuria; Apolipoproteins A; Apolipoproteins B; Blood Glucose; Blood Pressure; Body Composition; Body Constitution; Body Mass Index; C-Peptide; Cholesterol; Cross-Sectional Studies; Dietary Proteins; Female; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Obesity; Prevalence

We studied 112 type 2 diabetic patients. Fourteen patients had frank proteinuria, and 37 of the remaining 98 had microalbuminuria which was more frequent in men than in women (P < 0.02). Hypertension was found in 47 of the patients, equally distributed between sexes. Male diabetics with microalbuminuria had higher systolic blood pressure than diabetics without microalbuminuria (P < 0.02). Body mass index was higher in both sexes with hypertension compared to patients without hypertension. In the hypertensive men plasma C-peptide values were higher compared to patients without hypertension (P < 0.01) irrespective of the presence of microalbuminuria. A positive correlation between blood pressure and C-peptide was found (P < 0.01) in the men. We suggest that gender should be taken into account in the analysis and interpretation of microalbuminuria in type 2 diabetes.

Topics: Adult; Aged; Aged, 80 and over; Albuminuria; Blood Pressure; Body Mass Index; C-Peptide; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; Hypertension; Male; Middle Aged; Sex Factors

Insulin treatment of patients with type 2 diabetes causes hyperinsulinaemia and improves glycaemic control. We have studied how this affects risk factors for cardiovascular disease.. Patients with secondary failure to oral hypoglycaemic agents were studied whilst still taking oral agents and after insulin treatment for 8 weeks in an open study.. Department of Internal Medicine, University Hospital, Linköping.. Ten consecutive patients with type 2 diabetes and secondary failure to oral hypoglycaemic agents.. Switching oral treatment to insulin treatment.. Effect on several cardiovascular risk factors.. Fasting and postprandial plasma insulin concentrations were increased by insulin treatment whereas C-peptide concentrations were lowered. HbA1c was reduced from 8.9 +/- 0.3% (mean +/- SEM) to 6.3 +/- 0.2% after 8 weeks. There was a weight gain of 2.8 +/- 0.7 kg. Plasma concentrations of total- and very-low-density-lipoprotein (VLDL) cholesterol, VLDL-, low density lipoprotein and high-density-lipoprotein triglycerides were all reduced. The plasma concentration of apolipoprotein B was also lowered. Tissue plasminogen activator antigen measured after venous occlusion showed a significant reduction whilst plasminogen activator inhibitor 1 activity was 26.0 +/- 9.8 IU ml-1 on oral treatment and 18.2 +/- 4.7 IU ml-1 on insulin treatment (NS). Albumin excretion in the urine was reduced and the percentage reduction correlated with the percentage lowering of the tissue plasminogen activator antigen concentration after venous occlusion but not with the percentage change of basal tissue plasminogen activator antigen concentration.. Insulin treatment of patients with type 2 diabetes and secondary failure to oral hypoglycaemic agents causes hyperinsulinaemia and improves or has no unfavourable effect on several cardiovascular risk factors.

Topics: Adult; Aged; Albuminuria; Analysis of Variance; Blood Coagulation; Blood Glucose; Blood Pressure; C-Peptide; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Lipoproteins; Male; Middle Aged; Risk Factors

The study was designed to evaluate the urinary excretion of C-peptide and albumin, and urinary N-acetyl-beta-D-glucosaminidase (NAG) activity in juvenile borderline hypertensives. The second aim was to examine the relationship between these variables and ambulatory blood pressure level and variability. The study group consisted of 21 non-obese males consecutively chosen from patients with borderline hypertension, defined by sphygmanometer readings, examined in our outpatient clinic. All subjects collected separately their day-time and night-time urines during the period of ambulatory blood pressure monitoring. In 16 patients, who were considered to have "sustained" borderline hypertension, both 24-h urinary C-peptide excretion and 24-h UAE were significantly increased in comparison to those of the controls, while NAG activity did not differ significantly between the two groups. UAE was significantly lower at night than during the day in both borderline hypertensives and controls. Twenty-four-hour UAE in borderline hypertensives correlated significantly with the ambulatory blood pressure variability, but not with the average blood pressure level. These results suggest that the 24-h insulin secretion rate estimated by means of urinary C-peptide excretion is significantly increased in "sustained" borderline hypertensives. Elevated UAE in juvenile borderline hypertensives can be explained by a possible direct effect of systemic blood pressure variability on albuminuria.

Topics: Acetylglucosaminidase; Adult; Albuminuria; Blood Pressure; Blood Pressure Monitors; C-Peptide; Humans; Hypertension; Male

We examined the impact of hypertension and microalbuminuria on insulin sensitivity in patients with Type 2 (non-insulin-dependent) diabetes mellitus using the euglycaemic insulin clamp technique in 52 Type 2 diabetic patients and in 19 healthy control subjects. Twenty-five diabetic patients had hypertension and 19 had microalbuminuria. Hypertension per se was associated with a 27% reduction in the rate of total glucose metabolism and a 40% reduction in the rate of non-oxidative glucose metabolism compared with normotensive Type 2 diabetic patients (both p < 0.001). Glucose metabolism was also impaired in normotensive microalbuminuric patients compared with normotensive normoalbuminuric patients (29.4 +/- 2.2 vs 40.5 +/- 2.8 mumol.kg lean body mass-1.min-1; p = 0.012), primarily due to a reduction in non-oxidative glucose metabolism (12.7 +/- 2.9 vs 21.1 +/- 2.6 mumol.kg lean body mass-1.min-1; p = 0.06). In a factorial ANOVA design, however, only hypertension (p = 0.008) and the combination of hypertension and microalbuminuria (p = 0.030) were significantly associated with the rate of glucose metabolism. The highest triglyceride and lowest HDL cholesterol concentrations were observed in Type 2 diabetic patients with both hypertension and microalbuminuria. Of note, glucose metabolism was indistinguishable from that in control subjects in Type 2 diabetic patients without hypertension and microalbuminuria (40.5 +/- 2.8 vs 44.4 +/- 2.8 mumol.kg lean body mass-1.min-1). We conclude that insulin resistance in Type 2 diabetes is predominantly associated with either hypertension or microalbuminuria or with both.

Topics: Albuminuria; Blood Glucose; Blood Pressure; Body Mass Index; C-Peptide; Cholesterol; Cholesterol, HDL; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Fasting; Fatty Acids, Nonesterified; Glucagon; Glucose; Glycated Hemoglobin; Humans; Hypertension; Insulin; Insulin Resistance; Lipids; Liver; Middle Aged; Reference Values; Triglycerides

Topics: Albuminuria; Blood Glucose; Blood Pressure; C-Peptide; Cholesterol; Coronary Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Glycated Hemoglobin; Humans; Hyperinsulinism; Triglycerides

Microalbuminuria predicts cardiovascular events in diabetic and nondiabetic patients. For a better understanding of the physiopathological importance of microalbuminuria in atherosclerotic disease, we evaluated the relation between urinary albumin excretion and arterial blood pressure, left ventricular mass, insulin, and lipid levels. The studies were conducted in patients with atherosclerotic peripheral vascular disease. Urinary albumin excretion (studied by nephelometry; an average of triplicate collections from 8 PM to 8 AM), causal blood pressure, echocardiographic left ventricular mass index and wall thickness, plasma immunoreactive insulin and C-peptide (both basally and after a 75-g oral glucose load), blood lipids, and fibrinogen were studied in eight normal subjects and 20 nonobese, nondiabetic male patients with angiographically documented atherosclerotic peripheral vascular disease and preserved renal function, 12 of whom were either hypertensive or on antihypertensive treatment. Eight patients were microalbuminuric (urinary albumin > 20 micrograms/min) and 12 were not. Ankle-arm index and calf and foot transcutaneous oxygen tension were reduced in comparison with normal control subjects but superimposable between the two patient groups to indicate a comparable clinical progression of the vascular disease. In the microalbuminuric subjects, left ventricular mass index was greater, interventricular septum was thicker, and cardiac hypertrophy was more frequent than in nonmicroalbuminuric patients. The prevalence of hypertension tended to be greater and systolic blood pressure values were higher in the presence of microalbuminuria. Overall, a highly significant relation existed between urinary albumin excretion and left ventricular mass. Systolic blood pressure was greater and a history of arterial hypertension was more frequent among microalbuminurics, whereas diastolic blood pressure values showed a statistically significant correlation with both variables.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Aged; Albuminuria; Angiography; Arteriosclerosis; Blood Glucose; Blood Pressure; C-Peptide; Echocardiography; Fibrinogen; Glucose; Humans; Hyperinsulinism; Hypertrophy, Left Ventricular; Insulin; Lipids; Male; Middle Aged; Peripheral Vascular Diseases

The contribution from lipoproteins, blood pressure, albuminuria and demographic variables to coronary heart disease in 90 adult subjects with and 172 without Type 1 diabetes mellitus was examined in order to investigate whether risk factors were of equivalent importance in diabetic and non-diabetic coronary heart disease. Coronary heart disease (CHD) was present in roughly 25% of subjects in each group. In Type 1 diabetes those with CHD had significantly higher levels of systolic blood pressure, albumin excretion, serum creatinine, triglycerides, VLDL cholesterol and C-peptide, and reductions in serum concentrations of HDL and HDL2 cholesterol, in comparison to those without. However, the prevalence of smokers, and concentrations of Lp(a), ApoB and fibrinogen were comparable. Blood pressure and HDL cholesterol were higher in the CHD group with Type 1 diabetes in comparison to the nondiabetic group with CHD, although LDL concentrations and the prevalence of Lp(a) concentrations > 200 mg/l were lower. Logistic regression analysis revealed the strongest independent predictors of CHD in Type 1 diabetes were serum triglycerides, systolic blood pressure, age, serum LDL cholesterol, and the daily insulin dosage, whereas in the non-diabetic control group HDL2 cholesterol, Lp(a), ApoA1 and ApoB, total serum cholesterol and body mass index were additional predictors. CHD in Type 1 diabetes appears to be most closely associated with increasing age and levels of blood pressure and total serum lipids. Apolipoproteins and albuminuria did not seem to be important independent predictors of CHD in Type 1 diabetes, whereas the former were more clearly associated with CHD in non-diabetic controls.

Topics: Adult; Albuminuria; Alcohol Drinking; Apolipoproteins A; Apolipoproteins B; Blood Glucose; Blood Pressure; C-Peptide; Cholesterol, HDL; Cholesterol, VLDL; Coronary Disease; Creatinine; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Fibrinogen; Humans; Lipoprotein(a); Lipoproteins, HDL; Lipoproteins, LDL; Middle Aged; Regression Analysis; Risk Factors; Smoking; Triglycerides

OBJECTIVE--To assess kidney function and AER in patients with PD. RESEARCH DESIGN AND METHODS--Thirty-three patients with PD (age 52 +/- 7 yr, duration of disease 11 +/- 6 yr, BMI 24 +/- 3 kg/m2) and 33 patients with IDDM were matched for sex, BMI, and duration of disease. GFR and RPF were determined by single injection of [51Cr]EDTA and [125I]hippurate. AER was measured by radioimmunoassay in a single timed overnight urine collection. RESULTS--GFR and RPF were, respectively, 113 +/- 35 and 441 +/- 145 ml.min-1.73 m2 in patients with PD and 123 +/- 30 and 549 +/- 94 (P < 0.001) in IDDM. FF was significantly higher in patients with PD (0.26 +/- 0.05 vs. 0.22 +/- 0.03; P < 0.001). Prevalence of hyperfiltration (GFR > 135 ml.min-1.1.73 m2) was similar in both groups (30% in patients with PD vs. 28% in those with IDDM). Geometric mean of urinary AER was 10.4 micrograms/min (range 1-186) in patients with PD and 11.2 (1-198) in IDDM patients. Some 30.3% of patients with PD and 18% of those with IDDM were microalbuminuric (AER > 20 micrograms/min). By multiple regression analysis, AER was significantly related to systolic (P < 0.04) and diastolic blood pressure (P < 0.01) and to BMI (P < 0.03) in patients with PD. Retinopathy was more frequent in microalbuminuric patients with PD than in those without elevated AER. CONCLUSIONS--We suggest that early renal abnormalities occur similarly in patients with PD and IDDM.

Topics: Adult; Albuminuria; Body Mass Index; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Glomerular Filtration Rate; Humans; Kidney; Middle Aged; Pancreatic Diseases; Regional Blood Flow; Renal Circulation

The influence of albuminuria and proliferative retinopathy on concentration of serum lipoprotein (a) was examined cross-sectionally in 90 Type 1 diabetic patients. Concentrations of lipoprotein (a) were less in those with normoalbuminuria (90 (8-882) (median (range] U l-1) than in those with micro- or macro-albuminuria (137 (19-1722) U l-1, p less than 0.05). The prevalence of patients whose lipoprotein (a) concentrations were greater than 200 U l-1 was also greater (45% vs 24%, p = 0.03) among patients with albuminuria, but no difference was found between the microalbuminuric and macroalbuminuric groups (53 and 41%, respectively), or between those with or without proliferative retinopathy. The present finding that lipoprotein (a) concentrations may be increased at an early stage of diabetic renal disease may in part account for the excess ischaemic heart disease associated with diabetic nephropathy.

Topics: Albuminuria; Apolipoproteins B; Biomarkers; Blood Glucose; Blood Pressure; C-Peptide; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Coronary Disease; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Retinopathy; Female; Glycated Hemoglobin; Humans; Lipoprotein(a); Lipoproteins; Male; Middle Aged; Triglycerides; Vascular Diseases

The effect of residual C-peptide secretion in longer standing IDDM on glycaemic control and the prevalence and evolution of complications over 2 years was evaluated. Thirty-one subjects with IDDM of 15.4 (1.5) years duration (mean SEM)) and residual C-peptide secretion, were matched for age, duration of diabetes and body mass index with 31 subjects without detectable C-peptide secretion. At trial entry and over 2 years, levels of HbA1, fructosamine and mean blood glucose were essentially similar in both groups. Levels of glycated albumin (GSA) were significantly higher in the C-peptide negative group after 3 and 9 months (P less than 0.05). An increased prevalence of proliferative retinopathy in the C-peptide negative group and of peripheral vascular disease in the C-peptide secretor group was apparent at entry to the study (both P less than 0.05), although no significant differences were observed after 1 or 2 years. There was no difference in the prevalence of peripheral or autonomic neuropathy, hypertension, nephropathy or ischaemic heart disease. Subjects with C-peptide concentrations greater than 0.100 pmol/ml at entry to this study had lower daily insulin requirements after 1 and 2 years, but behaved like the larger group with any detectable C-peptide secretion in all other respects. Residual C-peptide secretion was lost after 1 year in 7 patients, in whom glycaemic control during the year had been particularly poor. Insulin antibody titres were no different in the 2 groups at any time point. This study suggests that residual C-peptide secretion in longer standing IDDM confers the potential for limited improvements in glycaemic control. This effect appears to be insufficient to prevent the evolution of microvascular complications over a 2-year period. Residual C-peptide secretion and relative hyperinsulinaemia may be associated with an excess of peripheral vascular disease.

Topics: Adult; Albuminuria; Biomarkers; Blood Glucose; Blood Glucose Self-Monitoring; Blood Pressure; C-Peptide; Coronary Disease; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Follow-Up Studies; Fructosamine; Glycated Hemoglobin; Hexosamines; Humans; Hypertension; Middle Aged

In order to evaluate the accuracy of urinary C-peptide determination and the clinical significance of C-peptiduria for the early course of insulin-dependent diabetes (IDDM), the rate of urinary excretion of C-peptide was determined in 32 children and adolescents with IDDM and correlated with serum C-peptide concentration, urinary excretion of albumin and beta 2-microgloublin and with the glomerular filtration rate (GFR) measured in terms of the clearance of 99mTc-DTPA. The age of the subjects ranged from 9.1 to 17.1 years (mean 13.1) and the duration of diabetes from 0.3 to 11.9 years (mean 4.6). There was a good correlation between postprandial serum C-peptide concentration and the 24-hour urinary C-peptide excretion rate (r = 0.81; p less than 0.001). GFR and urinary albumin excretion were slightly elevated in the diabetic patients as compared with non-diabetic subjects (p less than 0.05 and p less than 0.001, respectively), but C-peptide excretion was unrelated to the degree of hyperfiltration or albuminuria, neither was there any correlation between the excretion rate of beta 2-microglobulin and C-peptide. Glycaemic control was poorer in the diabetic children who had only trace amounts of C-peptide in their urine (less than 0.05 nmol/m2/24 h) than in those with minimal (0.05-1.0 nmol/m2) or moderate 24-hour urinary C-peptide excretion (greater than 1.0 nmol/m2). It is concluded that urinary C-peptide excretion serves very well to reflect residual beta-cell function and is unrelated to the slight renal hyperfunction and albuminuria often seen in diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Age Factors; Albuminuria; beta 2-Microglobulin; C-Peptide; Child; Diabetes Mellitus, Type 1; Female; Glomerular Filtration Rate; Humans; Male; Reference Values; Sex Factors; Time Factors

The aim of the present study was to evaluate the role of residual insulin production in long-term Type 1 (insulin-dependent) diabetes mellitus. Ninety-seven patients with a disease duration of 9-16 years and onset before the age of 30 years were studied. C-peptide excretion in 24-h urine samples was measured as an indicator of residual insulin production. Thirty-five patients (36%) excreted C-peptide (greater than or equal to 0.2 nmol); as many as possible of them were carefully matched with a non-excretor patient with regard to age at onset of diabetes and disease duration. Twenty-nine pairs were obtained, and 22 of them agreed to participate in further investigations of glycaemic control and microangiopathic lesions. The patients who excreted C-peptide had significantly lower HbA1c than the non-excretor group, 6.9 +/- 0.3% vs 7.9 +/- 0.3%, (p less than 0.025). Moderate-to-advanced background retinopathy was found in 2 patients in the excretor group and in 7 patients in the non-excretor group. Microalbuminuria [ratio of albumin: creatinine (mg/l:mmol/l) greater than or equal to 5] was found in 1 and in 5 patients, respectively, while proteinuria [ratio of protein: creatinine (mg/l:mmol/l X 10) greater than or equal to 136] was found in 0 and in 4 patients, respectively. Microalbuminuria and/or proteinuria was found in 7 of the non-excretor group as compared to 1 in the excretor group (p = 0.046).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Albuminuria; beta 2-Microglobulin; Blood Pressure; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Secretion; Male; Proteinuria

To evaluate the interpretation of different kidney function tests in diabetic children and teenagers we have studied 47 children with a duration of diabetes up to 5 years, 61 children with a duration of 5.1-10 years and 49 children with a duration of greater than 10 years. Glomerular filtration rate (GFR) measured as inulin clearance or creatinine clearance, clearance PAH (CPAH), filtration fraction (FF), 24-hour urinary excretion of beta 2-microglobulin and albumin were examined and correlated with short- and longterm indices of metabolic control. In all groups of duration GFR as measured by inulin clearance was increased compared with reference values from age matched controls. In patients who had had diabetes for 0-5 years a significant positive correlation was found between inulin clearance and blood glucose during the examination. Inulin clearance was also correlated to HBA1c as well as to 24-hour urinary glucose (mean of 4-6 samples during two years). No such correlation was found in the group who had had diabetes for 5-10 years but in patients with a duration of diabetes greater than 10 years a significant inverse relation was found between GFR and HbA1c. The 24-hour urinary excretion of albumin was significantly higher in all groups of diabetics compared with controls. The urinary excretion of beta 2-microglobulin was similar in diabetics and controls. In the total material no significant correlation could be found between inulin clearance and creatinine clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Albuminuria; beta 2-Microglobulin; Blood Glucose; C-Peptide; Child; Creatinine; Diabetes Mellitus, Type 1; Fatty Acids, Nonesterified; Glomerular Filtration Rate; Glycosuria; Humans; Hydroxybutyrates; Kidney; Prospective Studies