c-peptide and Proteinuria

Kidney disease remains a major cause of morbidity and mortality in Canada and worldwide. New medical treatments are needed to reduce the progression of kidney disease to improve patient outcomes. C-peptide is normally released by pancreatic beta-cells along with insulin in healthy individuals, and has been shown to have intrinsic biological activity and to potentially be renoprotective. The effect of exogenous C-peptide on kidney structure and function, and the role of C-peptide in the treatment of kidney disease have not yet been fully elucidated.. We will conduct a systematic review of the literature in human clinical trials and mammalian experimental models to ascertain the current evidence for the role of C-peptide as a potential therapeutic agent for the treatment of kidney disease. We aim to identify whether exogenously delivered C-peptide has an effect on clinically relevant outcomes such as glomerular filtration rate, proteinuria, kidney histology, requirement of renal replacement therapy, and mortality. We will search MEDLINE, EMBASE, and the Cochrane Central Databases for human or animal studies in which C-peptide was administered and renal endpoints were subsequently measured. Study quality will be assessed using the Cochrane Collaboration's tool for assessing risk of bias. If appropriate, a meta-analysis will be performed as per standard techniques.. The results of this study will determine the potential role of C-peptide as a therapeutic intervention for patients with kidney disease and will help guide subsequent clinical trials. The study may also provide insight into which patients or disease states are likely to benefit the most from C-peptide.. PROSPERO CRD42014007472.

Topics: C-Peptide; Glomerular Filtration Rate; Humans; Kidney; Kidney Diseases; Proteinuria; Systematic Reviews as Topic; Treatment Outcome

A growing body of evidence supports the concept that treatment with the newer angiotensin type-1 receptor blockers (ARBs) improves glucose homeostasis under conditions wherein it is impaired. Controversy exists, however, regarding the ability of losartan, an older ARB, to exert comparable improvement. The present study was undertaken to evaluate the effects of losartan on glucose homeostasis in subjects with type 2 diabetes and nephropathy.. Twenty-seven subjects with type 2 diabetic nephropathy were enrolled in this prospective, randomized, controlled study. Losartan (100 mg daily) or the calcium channel blocker amlodipine (10 mg daily) was administered for a period of 3 months. Fasting blood glucose, serum insulin and C-peptide concentrations were measured at baseline and at the end of the study. Oral glucose tolerance tests were performed to evaluate insulin sensitivity and beta-cell responsiveness. Insulin resistance was measured using the homeostasis model assessment of insulin resistance (HOMA-IR).. Fasting blood glucose, HbA1c, AUC glucose, and urinary protein values were significantly decreased in the losartan group as compared with the amlodipine group (P<0.05). Furthermore, C-peptide concentrations, the insulin sensitivity index, and the insulin-to-glucose ratio were significantly increased after 3 months of therapy with losartan as compared to amlodipine (P<0.05). Reductions of fasting insulin concentrations and HOMA-IR were also observed for the losartan group; however, reductions were not significant when compared with the amlodipine group.. In addition to reducing urinary protein excretion, losartan at 100 mg daily increases insulin sensitivity and improves glucose homeostasis in subjects with type 2 diabetic nephropathy.

Topics: Adult; Aged; Amlodipine; Angiotensin II Type 1 Receptor Blockers; Blood Glucose; C-Peptide; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Fasting; Female; Glycated Hemoglobin; Homeostasis; Humans; Insulin; Insulin Resistance; Losartan; Male; Middle Aged; Proteinuria; Time Factors; Treatment Outcome

Pancreas transplant alone can be effective in significantly improving the quality of life of type 1 diabetic patients, and it can also eliminate acute diabetes complications, such as hypoglycemic and/or hyperglycemic episodes. The effects of pancreas transplant alone on long-term complications of diabetes, including nephropathy, are still not settled. We evaluated whether restoration of long-lasting normoglycemia by pancreas transplant alone might have beneficial action on diabetic nephropathy.. A total of 32 type 1 diabetic patients were evaluated before and 1 year after successful pancreas transplant alone, together with 30 matched nontransplanted type 1 diabetic subjects. Several metabolic and kidney function parameters were measured, including plasma glucose, glycohemoglobin (A1C), C-peptide, plasma lipids, blood pressure, creatinine, creatinine clearance, and urinary protein excretion.. Pancreas transplant alone restored sustained normoglycemia, without exogenous insulin administration, and improved plasma lipid levels. Blood pressure decreased significantly. Creatinine concentrations and clearances did not differ before and after transplantation. Urinary protein excretion decreased significantly after pancreas transplant alone, with four microalbuminuric and three macroalbuminuric patients who became normoalbuminuric. None of these changes occurred in the nontransplanted group.. Successful pancreas transplant alone, through restoration of sustained normoglycemia, improves diabetic nephropathy in type 1 diabetic patients.

Topics: Adult; Anticholesteremic Agents; Antihypertensive Agents; Blood Glucose; C-Peptide; Cholesterol; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Follow-Up Studies; Humans; Male; Pancreas Transplantation; Proteinuria; Time Factors; Triglycerides

C-peptide is a reliable marker of beta cell reserve and is associated with diabetic complications. Furthermore, HbA1c level is associated with micro- and macro-vascular complications in diabetic patients. HbA1c measurement of diabetic patients with anemia may be misleading because HbA1c is calculated in percent by taking reference to hemoglobin measurements. We hypothesized that there may be a relationship between C-peptide index (CPI) and proteinuria in anemic patients with type 2 diabetes mellitus (T2DM). Therefore, the aim of the present study was to investigate the association between C-peptide levels and CPI in anemic patients with T2DM and proteinuria.. The patients over 18 years of age with T2DM whose C-peptide levels were analyzed in Endocrinology and Internal medicine clinics between 2014 and 2018 with normal kidney functions (GFR>60 ml/min) and who do not use any insulin secretagogue oral antidiabetic agent (i.e. sulfonylurea) were enrolled into the study.. Hemoglobin levels were present in 342 patients with T2DM. Among these 342 cases, 258 (75.4%) were non-anemic whereas 84 (24.6%) were anemic. The median DM duration of the anemic group was statistically significantly higher in T2DM (p=0.003). There was no statistically significant difference found in proteinuria prevalence between non-anemic and anemic patient groups (p=0.690 and p=0.748, respectively). Anemic T2DM cases were corrected according to the age, gender, and duration of DM. C-peptide and CPI levels were not statistically significant to predict proteinuria (p=0.449 and p=0.465, respectively).. The present study sheds light to the association between C-peptide, CPI, and anemic diabetic nephropathy in T2DM patients and indicates that further prospective studies are needed to clarify this issue.

Topics: Adult; Aged; Anemia; Biomarkers; C-Peptide; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Hemoglobins; Humans; Male; Middle Aged; Proteinuria; Retrospective Studies; Time Factors

Topics: Blood Flow Velocity; Blood Pressure; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Glycated Hemoglobin; Humans; Kidney Transplantation; Pancreas Transplantation; Prospective Studies; Proteinuria; Retinal Artery; Uremia

Recent experimental and clinical data suggest that C-peptide replacement during type 1 diabetes exerts beneficial effects on diabetic nephropathy. The aim of this study was to determine if physiological C-peptide administration in replacement dose during 28 days had beneficial effects on metabolic status and renal functions in type-1 diabetic rats.. Four groups of rats were investigated: a non diabetic group treated with buffer (C group, n=6), three streptozotocin diabetic-induced groups treated with either buffer (D group, n=6), insulin (D-I group, n=6) or rat homologous C-peptide (D-C group, n=6). Weight gain was measured every week. All animals were housed in metabolic cages on day 28 for assessment of metabolic data. Blood and urine samples were collected to allow measurement of plasmatic osmolality, C-peptide concentration, sodium, and glucose losses and proteinuria. Glomerular filtration rate (GFR) was determined by creatinine clearance.. All streptozotocin-treated animals were diabetic. Glycaemic control (mg/dl), was markedly improved in D-I (133+/-65) when compared with either D (547+/-49, P<0.05) or D-C (520+/-48, P<0.05) groups. Conversely, weight gain during the study, was improved in D-I and D-C as compared with D animals (135+/-13 and 41+/-18 vs 18+/-21 respectively), despite different glycaemic control. Diabetes-induced glomerular hyperfiltration (ml/min/kg), urinary protein leakage (g/kg/day), and Na urinary losses (mmol/100 g/day) respectively, were significantly (P<0.05) reduced in D-C (3.95+/-0.6; 0.08+/-0.06; 1.5+/-0.9) in comparison with D (4.95+/-0.8; 0.18+/-0.16; 3.7+/-2.1) and D-I (5+/-0.9; 0.19+/-0.11; 2.7+/-0.8) animals. Plasmatic osmolality was significantly increased in D group whereas there were no differences between C group and D-C group. Food and water intakes, urinary volume as well as urinary glucose losses were not significantly different between D-C and D groups.. C-peptide administration in replacement dose to streptozotocin diabetic rats induces weight gain regardless hyperglycaemia or glycosuria. Diabetic animals supplemented with C-peptide exhibit better renal function resulting in reduced urinary sodium waste and protein excretion together with reduction of the diabetes-induced glomerular hyperfiltration.

Topics: Animals; Blood Glucose; C-Peptide; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Insulin; Kidney; Male; Proteinuria; Rats; Rats, Sprague-Dawley; Sodium; Weight Gain

To determine serum leptin levels in hypertensive disorder of pregnancy.. In this prospective, cross-sectional, case control study, we measured serum leptin levels of 58 hypertensive pregnant women and 54 normal pregnant women. We also did blood and urine analysis for the evaluation of the severity of hypertensive disorder of pregnancy. The patients were followed until after delivery and information about labour was recorded. We analysed the difference and correlation between anthropometric measures, hormonal and biochemical parameters, and serum leptin levels in two groups.. In the study group, serum leptin levels were determined to be higher than the control group. Neonatal birth weight was significantly lower in the hypertensive group. While the serum uric acid, urea, aspartate aminotransferase, fibronectin, and fasting blood glucose levels were found to be higher, serum total protein and albumin levels were significantly lower among the hypertensive pregnant women. Hypertensive pregnant women were more insulin resistant. Serum leptin levels were highly and positively correlated with serum fibronectin, and C peptide levels. A negative significant correlation was observed between maternal serum leptin levels and neonatal birth weight among the pregnant women having the hypertensive disorders.. Serum leptin levels in hypertensive pregnant women appear to be higher. The determination of serum leptin levels may be as important as serum fibronectin and C peptide levels in the management of hypertensive disorder of pregnancy. C peptide and insulin may be due to hyperinsulinemia which leads to increased stimulation of leptin production by fatty tissue. Insulin resistance which appears in late pregnancy is more significant especially in pregnancies complicated by preeclampsia.

Topics: Birth Weight; Body Mass Index; C-Peptide; Cross-Sectional Studies; Female; Fibronectins; Humans; Hypertension, Pregnancy-Induced; Insulin Resistance; Leptin; Logistic Models; Pregnancy; Prospective Studies; Proteinuria; Skinfold Thickness

Recent studies suggested that C-peptide treatment of C-peptide-deficient patients with type I diabetes mellitus may present a new approach to prevent diabetic nephropathy. The present study further elucidated this concept by assessing the acute effect of human C-peptide application on kidney function in anesthetized rats with streptozotocin (STZ)-induced diabetes. Human C-peptide was applied as an i.v. bolus followed by continuous infusion of a fivefold dose per hour. A dose of 6 nmol/kg plus 30 nmol/kg per h is referred to as 1x. Application of 0.1, 0.3, 1, 3 or 10x to STZ-diabetic rats elicited mean plasma human C-peptide concentrations of 0.5, 5, 24, 75 and 225 nmol/l, respectively. Under basal conditions STZ-diabetic rats exhibited as expected an increase in glomerular filtration rate (GFR) by about 30%, which was associated with a lower total renal vascular resistance (RVR) and a rise in renal blood flow (RBF) as well as enhanced urinary protein excretion (UPE) of about 70% as compared with control rats. Human C-peptide dose-dependently lowered GFR and UPE in STZ-diabetic rats without altering blood glucose levels. No significant effect of human C-peptide on RBF or RVR could be detected, which may indicate an effect on glomerular ultrafiltration coefficient. Maximum effects of human C-peptide on the diabetes-induced rises in GFR and UPE established an inhibition of 40% and 50%, respectively. Half-maximum effects on GFR and UPE were observed at plasma concentrations of human C-peptide in the range of 0.5-5 nmol/l, which is relatively close to endogenous C-peptide levels in non-diabetic rats. Unresponsiveness of non-diabetic control rats to human C-peptide further indicated specific effects.

Topics: Animals; C-Peptide; Diabetes Mellitus, Experimental; Dose-Response Relationship, Drug; Glomerular Filtration Rate; Humans; Kidney Function Tests; Male; Proteinuria; Rats; Rats, Sprague-Dawley

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

To learn if Hispanic people with type 2 diabetes have excess incidence and/or progression of diabetic retinopathy and to explore the association of risk factors with diabetic retinopathy.. There were 244 subjects with type 2 diabetes (65.3% Hispanic) with at least one follow-up visit between 1984 and 1992 examined for the development of retinopathy over a median of 4.8 years (range 2.0-6.6 years). Stereo fundus photos were graded by the University of Wisconsin Reading Center.. Of the 169 subjects without retinopathy at baseline, 47 developed some retinopathy, an incidence rate of 63.7 per 1,000 person-years (PY), or a 4-year cumulative incidence of 22.5%. The Hispanic incidence rate was 58.3/1,000 PY (95% CI: 39.4-83.3), which was lower than among non-Hispanic whites, 76.1/1,000 PY (44.3-121.9). Progression occurred in 24 of the 75 subjects with retinopathy at baseline, a 4-year cumulative rate of 24.1%. Logistic regression showed that insulin treatment was associated with higher risk of any retinopathy (odds ratio [OR] = 8.45, 2.65-26.97), and both systolic blood pressure (odds ratio [OR] = 1.58, 0.99-2.52) and total GHb (OR = 1.46, 0.99-2.17) nearly attained statistical significance. After adjustment for multiple potential risk factors, the Hispanic/non-Hispanic white OR was 0.66 (0.28-1.57).. No excess risk for incident retinopathy was found among Hispanic compared with non-Hispanic white subjects in this population. These results are consistent with our previously reported prevalence data from the same population but differ from reports of excess prevalence among Texas Hispanics. No other Hispanic incidence data are available to assist in reconciling this difference.

Topics: Blood Pressure; Body Mass Index; C-Peptide; Cholesterol; Cholesterol, HDL; Colorado; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Disease Progression; Ethnicity; Female; Follow-Up Studies; Hispanic or Latino; Humans; Incidence; Male; Middle Aged; Prevalence; Proteinuria; Risk Factors; Smoking; Time Factors; Triglycerides; White People

Sex hormones are associated with atherogenic changes in lipoproteins and changes in glucose and insulin metabolism, yet few data are available on the relationship of sex hormones and dehydroepiandrosterone sulfate (DHEA-SO4) to ischemic heart disease (IHD) in diabetic subjects, a group with very high levels of IHD.. We examined the relation of total and free testosterone, sex hormone binding globulin, estrone, estradiol, and DHEA-SO4 to the 5-year IHD mortality in the older-onset diabetic subjects in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) in a matched diabetic subject-control design (two control subjects for every diabetic subject).. In men (n = 123), none of the sex hormones or DHEA-SO4 significantly predicted IHD mortality. In women (n = 120), lower levels of DHEA-SO4 (P < 0.01) and total testosterone (P = 0.07) predicted IHD mortality. These results were essentially unchanged after adjustment for duration of diabetes, GHb, diuretic use, and serum creatinine, which are major predictors of IHD mortality in the WESDR. Finding lower testosterone levels in diabetic subjects of IHD in women is contrary to data on risk factors, which suggests that increased androgen activity may be associated with worse IHD risk factors.. This study suggests that alterations in sex hormones and DHEA-SO4 are unlikely to explain a major proportion of the variation in IHD mortality in diabetic subjects.

Topics: Adult; Age of Onset; Aged; Biomarkers; C-Peptide; Cross-Sectional Studies; Dehydroepiandrosterone Sulfate; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Retinopathy; Estradiol; Estrone; Female; Humans; Hypertension; Male; Middle Aged; Myocardial Ischemia; Predictive Value of Tests; Proteinuria; Sex Characteristics; Sex Hormone-Binding Globulin; Smoking; Testosterone; Wisconsin

Topics: Adenine; Adult; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Family; Female; Glucose Clamp Technique; Glycated Hemoglobin; Guanine; Hearing Loss; Humans; Insulin; Male; Middle Aged; Point Mutation; Polymerase Chain Reaction; Proteinuria; RNA; RNA, Mitochondrial; RNA, Transfer, Leu

The relationship between plasma C-peptide and the 6-year incidence and progression of diabetic retinopathy was examined in a population-based study in Wisconsin. Individuals with younger-onset (n = 548) and older-onset (n = 459) diabetes were included. C-peptide was measured by radioimmunoassay with Heding's M1230 antiserum. Retinopathy was determined from stereoscopic fundus photographs. Younger- and older-onset insulin-using individuals with undetectable or low plasma C-peptide (< 0.3 nmol/l) at baseline had the highest incidence and rates of progression of retinopathy, whereas older-onset individuals with C-peptides > 0.3 nmol/l had the lowest incidence and rates of progression of retinopathy. However, within each group (younger-onset using insulin, older-onset using insulin, and older-onset not using insulin), after we controlled for other characteristics associated with retinopathy, there was no relationship between higher levels of C-peptide at baseline and lower 6-year incidence or progression of retinopathy. These data suggest that glycemic control, and not C-peptide, is related to the incidence and progression of diabetic retinopathy.

Topics: Adult; Age of Onset; Biomarkers; Blood Pressure; Body Mass Index; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Disease Progression; Female; Glycated Hemoglobin; Humans; Incidence; Insulin; Male; Obesity; Proteinuria; Wisconsin

Parameters of fibrinolysis, including basal plasma tissue type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) antigen levels were studied in 49 non-insulin dependent diabetic patients (23 men, 26 women: ages 51.3 +/- 14.9 years) and 16 age matched non-diabetic subjects (9 men, 7 women ages 49.8 +/- 12.2 years) as a control group. Compared to a control group, the diabetic patients had a significantly higher mean plasma t-PA antigen (4.94 +/- 2.68 vs 3.20 +/- 2.30 ng/ml) and PAI-1 antigen (34.86 +/- 16.71 vs. 17.60 +/- 15.36 ng/ml) levels (P < 0.05). Significant univariate correlations were observed between t-PA and body mass index (BMI) (P = 0.0009, r = 0.7217), and PAI-1 were positively correlated with BMI and FBS (fasting blood sugar) in the total diabetic patients (P = 0.0003, r = 0.7217; P = 0.0477, r = 0.2858, respectively). In diabetic patients with proliferative diabetic retinopathy, both PAI-1 and t-PA antigen levels were significantly lower than those of diabetic patients with negative or background retinopathy (P = < 0.05). There were no significant differences of the plasma t-PA and PAI-1 levels between diabetic patients with micro- and macroproteinuria. This study conducted on non-insulin dependent diabetic patients suggests that they have significantly higher t-PA and PAI-1 antigen levels than do control subjects, and these findings appear to correlate negatively with proliferative retinopathy observed among the patients studied.

Topics: Analysis of Variance; Blood Glucose; Body Mass Index; C-Peptide; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Enzyme-Linked Immunosorbent Assay; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Proteinuria; Reference Values; Tissue Plasminogen Activator; Triglycerides

This study attempted to determine whether postprandial hypotension (PPH) is associated with diabetes mellitus by 24-h ambulatory blood pressure monitoring (24-h ABPM) and by monitoring blood pressure during 75-g oral glucose tolerance test (75-g OGTT) in 15 normal subjects and 35 patients with non-insulin-dependent diabetes mellitus. When we defined PPH as a postprandial decrease in systolic blood pressure of greater than 20 mmHg, the incidence of PPH in diabetics was 37% by 24-h ABPM and 20% by 75-g OGTT. The incidence of proliferative retinopathy and proteinuria was greater in diabetics with PPH than in those without PPH. All of the patients with PPH had somatic and autonomic neuropathy. The C-peptide response was lower in diabetics with PPH than in those without PPH. We revealed the presence of PPH in diabetics, and found that PPH was closely related to disease severity, especially diabetic autonomic neuropathy.

Topics: Adult; Blood Glucose; Blood Pressure; C-Peptide; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Diabetic Retinopathy; Diastole; Eating; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Hypotension; Middle Aged; Monitoring, Physiologic; Norepinephrine; Proteinuria; Reference Values; Systole

The variation of urinary C-peptide clearance in relation to hyperglycemia and renal damage was evaluated in 57 patients with non-insulin-dependent diabetes mellitus (NIDDM) with and without overt proteinuria, 14 nondiabetic patients with renal disease (RD) and 18 healthy control subjects. Urinary C-peptide clearance expressed as the ratio of urinary C-peptide to creatinine clearance (CCP/CCR) in the fasting state did not differ in control subjects and RD patients, and was higher equally in NIDDM patients with and without proteinuria. In NIDDM patients without overt proteinuria, urinary levels of C-peptide, beta 2-microglobulin (B2M), N-acetyl-beta-D-glucosaminidase (NAG) and albumin as well as CCP/CCR ratio all decreased significantly with short-term glycemic control (P less than 0.05). Despite a wide range of CCP/CCR ratio (0.07-0.73), a weak but significant correlation (r = 0.56, P less than 0.005) was found between fasting serum and urinary C-peptide levels in NIDDM patients. These results suggest that urinary C-peptide may easily be affected by hyperglycemia per se rather than renal damage, while urinary B2M, NAG and albumin may be affected by both hyperglycemia and renal damage. When the urinary C-peptide level is interpreted, the influence of hyperglycemia on it must be taken into consideration.

Topics: Acetylglucosaminidase; beta 2-Microglobulin; Biomarkers; C-Peptide; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Humans; Hyperglycemia; Kidney Diseases; Male; Middle Aged; Proteinuria; Reference Values

Recent data suggest genetic contributions to the microvascular complications of Type 1 (insulin-dependent) diabetes mellitus. Most research has focused on the HLA region, and the potential role of other genetic loci has not been adequately explored. We examined the possible relationship between DNA polymorphisms in the region 5' to the insulin gene on chromosome 11 and diabetic nephropathy. This was done by comparison of those diabetic patients homozygous for class 1 alleles at the 5' insulin gene polymorphism locus to 1/3 heterozygotes in a well-characterized series of 324 insulin-requiring diabetic patients from the Wisconsin Epidemiologic Study of Diabetic Retinopathy. Proteinuria (defined as greater than or equal to 0.3 g protein/l urine), was used as suggestive evidence for diabetic nephropathy. Hypertension, a frequent associated finding in diabetic patients with nephropathy, was defined as a blood pressure greater than 140/90 or a history of previous treatment of hypertension. The two genotypically defined groups did not differ from each other in regard to sex ratio, age at diagnosis, age at examination, duration of diabetes, body mass, HbAlc or C-peptide. The 1+1 group had a higher prevalence of proteinuria, 29% as compared to 16.2% in other genotypes (p less than 0.05). There was no significant difference in the frequency of hypertension between the two genotypic groups. This finding suggests that the 5' insulin gene polymorphism may be associated with risk for nephropathy, but the pathophysiologic mechanism remains unclear.

Topics: Blood Pressure; C-Peptide; Chromosome Mapping; Chromosomes, Human, Pair 11; Cohort Studies; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Retinopathy; Female; Genes; Glycated Hemoglobin; Humans; Hypertension; Insulin; Male; Polymorphism, Genetic; Proteinuria; Sex Characteristics

In 38 diabetic patients, admitted on a long-term basis to a nursing home, the clinical situation and presence of secondary diabetic complications were assessed, and their macrovascular complications and degree of glycemic control compared with those in ambulatory diabetic patients, matched for age, sex, known duration of diabetes and specific antidiabetic therapy. No differences in blood glucose control, plasma triglycerides, blood pressure and serum creatinine were observed between both groups of patients. Plasma cholesterol levels were higher in the ambulatory patients (6.4 +/- 1.0 vs 5.6 +/- 1.1 mmol/l, P = 0.008). Twenty-two nursing home patients had suffered from stroke, against 4 ambulatory patients. Hypertension was found in almost 50% of all patients, whereas its prevalence was highest in the stroke patients (69 vs 36%, P less than 0.01). In the nursing home patients, peripheral vascular abnormalities, skin necrosis or leg ulcers and recurrent urinary tract infections were frequently encountered, whereas in the ambulatory patients cardiac complaints were more prevalent. Use of medication, especially diuretics and anticoagulant agents, was higher in the nursing home patients. Diabetes and the sequelae of its macrovascular complications may greatly impair the quality of life of the diabetic patient, and place a large financial and personal burden on the health care in general. Better identification of diabetic patients with a high risk of stroke is necessary.

Topics: Aged; Ambulatory Care; Blood Glucose; Blood Pressure; C-Peptide; Cerebrovascular Disorders; Diabetes Complications; Diabetes Mellitus; Diet, Diabetic; Female; Fructosamine; Glycated Hemoglobin; Hexosamines; Homes for the Aged; Humans; Hypertension; Hypoglycemic Agents; Insulin; Lipids; Long-Term Care; Male; Nursing Homes; Proteinuria

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

In an 11-year study of experimental insulin-deficient diabetes (IDDM) induced in rhesus monkeys by streptozotocin or total pancreatectomy, the authors have found that pathophysiologic changes occur in eye and kidney, which closely resemble the early stages of human insulin deficient diabetes mellitus (IDDM). In addition, morphologic changes of thickening of glomerular capillary basement membrane and expansion of mesangial matrix (by light microscopy) appear within 3 years of onset of hyperglycemia. However, progression to irreversible complications of advanced diabetic nephropathy or proliferative retinopathy, have not occurred. This animal model resembles human disease in that the animals tend to become ketotic unless maintained with exogenous insulin; C-peptide production is low to absent, and large amounts of glycosylated hemoglobin develop within a month of onset. The monkeys differ from humans in the absence of hypertension and hyperlipidemia. The authors suggest that the abnormalities in basement membrane form and function caused by hyperglycemia form the necessary background upon which other factors, such as hypertension and hyperlipidemia, then act to cause irreversible complications. The role of pancreatic transplantation is in prevention of these background changes.

Topics: Animals; Blood Glucose; Blood Pressure; C-Peptide; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Diabetic Retinopathy; Eye; Glycated Hemoglobin; Hypertrophy; Kidney; Macaca mulatta; Pancreas Transplantation; Proteinuria