c-peptide and Glycosuria

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Retinopathy; Glycated Hemoglobin; Glycosuria; Humans; Hypoglycemia; Insulin; Insulin Infusion Systems; Insulin Secretion; Time Factors

In two groups of pts with diabetic derangements the effect of infusion therapy was investigated with regard to metabolic and endocrine functions. The rate of infusion was adapted to the height of the central venous pressure and the administration of electrolytes to their serum concentration. Insulin was withheld until no further decrease of blood glucose was noted. Group A consisted of 8 pts with severe diabetic ketoacidosis (blood glucose higher than 25 mmol/l, pH below 7.0 and/or bicarbonate below 10 mmol/l). The duration of insulinfree rehydration was 8.8 +/- 1.3 (x +/- SE) hrs and the fluid retention 4060 +/- 3 633 ml. The osmolality in serum decreased from 356 +/- 12 to 340 +/- 8 mosm/kg H2O and the blood glucose from 37.9 +/- 2.9 to 28.6 +/- 3.4 mmol/l. No correlation existed between the decrease of blood glucose and the expansion of the intravascular volume. Therefore, the decrease of blood glucose was not caused by a simple dilution effect. High renal glucose excreation was observed (408 +/- 83 mmol) but could not explain the decrease of blood glucose. The glucose clearance fell from 25.9 +/- 6.9 to 21.5 +/- 3.8 ml/min/1.73 m2 body surface from the first to the last 2-hr periods. It must be concluded that the initial rehydration deminished gluconeogeneses and/or increased tissue glucose utilization without exogenous insulin administration. This conclusion is supported by the decrease in the plasma concentration of the contrainsular hormons. Glucagon decreased 579 +/- 209 to 319 +/- 88 pg/ml (n.s.). Cortisol from 49.9 +/- 4.6 to 35.8 +/- 6.7 micrograms/100 ml (p < 0.05) and Adrenalin from 2.43 +/- 1.03 to 0.4 +/- 0.22 ng/ml (p < 0.05). Blood gas analysis revealed only minimal and ketobodies in serum no changes. Therefore, it can be concluded that rehydration and decrease of plasma concentration of contrainsular hormones do not influence the enhenced lipolyses in diabetic ketoacidosis. Group B consisted of 8 pts with nonacidotic diabetic derangements (blood glucose higher than 25 mmol/l, pH above 7.3 and/or bicarbonate above 18 mmol/l) and an acute weightloss of more than 3 kg. The insulinfree rehydration lasted 13 +/- 1.6 hrs and the fluid retention was 4620 +/- 380 ml. The serum osmolality decreased from 317 +/- 5.3 to 288 +/- 1.9 mmol/l. The decrease of blood glucose could not be explained by delution effect. The renal glucose excreation was 370 +/- 120 mmol/l in total and the glucose clearance decreased from 15.3 +/- 8.4 to 8.0 +/- 2.8 ml/min/1.

Topics: Acidosis; Adolescent; Adult; Aged; Aldosterone; Blood Glucose; C-Peptide; Diabetes Mellitus; Electrolytes; Epinephrine; Female; Glucagon; Gluconeogenesis; Glycosuria; Humans; Hydrocortisone; Hydrogen-Ion Concentration; Infusions, Parenteral; Insulin; Male; Middle Aged; Osmotic Pressure; Renin; Water-Electrolyte Balance

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Dietary Carbohydrates; Glucose Tolerance Test; Glycosuria; Humans; Insulin; Ketone Bodies; Lipid Metabolism; Proteins; Radioimmunoassay

To examine whether lowering plasma glucose concentration with the sodium-glucose transporter-2 inhibitor empagliflozin improves β-cell function in patients with type 2 diabetes mellitus (T2DM).. Patients with T2DM (N = 15) received empagliflozin (25 mg/d) for 2 weeks. β-Cell function was measured with a nine-step hyperglycemic clamp (each step, 40 mg/dL) before and at 48 hours and at 14 days after initiating empagliflozin.. Glucosuria was recorded on days 1 and 14 [mean ± standard error of the mean (SEM), 101 ± 10 g and 117 ± 11 g, respectively] after initiating empagliflozin, as were reductions in fasting plasma glucose levels (25 ± 6 mg/dL and 38 ± 8 mg/dL, respectively; both P < 0.05). After initiating empagliflozin and during the stepped hyperglycemic clamp, the incremental area under the plasma C-peptide concentration curve increased by 48% ± 12% at 48 hours and 61% ± 10% at 14 days (both P < 0.01); glucose infusion rate increased by 15% on day 3 and 16% on day 14, compared with baseline (both P < 0.05); and β-cell function, measured with the insulin secretion/insulin resistance index, increased by 73% ± 21% at 48 hours and 112% ± 20% at 14 days (both P < 0.01). β-cell glucose sensitivity during the hyperglycemic clamp was enhanced by 42% at 14 hours and 54% at 14 days after initiating empagliflozin (both P < 0.01).. Lowering the plasma glucose concentration with empagliflozin in patients with T2DM augmented β-cell glucose sensitivity and improved β-cell function.

Topics: Adult; Benzhydryl Compounds; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Glucose Clamp Technique; Glucosides; Glycosuria; Humans; Hypoglycemic Agents; Insulin Resistance; Insulin-Secreting Cells; Male; Middle Aged

Several studies have demonstrated that diabetic patients with cirrhosis require insulin treatment because of insulin resistance. As chronic alcoholic liver damage is partly due to the lipoperoxidation of hepatic cell membranes, anti-oxidizing agents may be useful in treating or preventing damage due to free radicals. The aim of this study was to ascertain whether long-term treatment with silymarin is effective in reducing lipoperoxidation and insulin resistance in diabetic patients with cirrhosis.. A 12-month open, controlled study was conducted in two well-matched groups of insulin-treated diabetics with alcoholic cirrhosis. One group (n=30) received 600 mg silymarin per day plus standard therapy, while the control group (n=30) received standard therapy alone. The efficacy parameters, measured regularly during the study, included fasting blood glucose levels, mean daily blood glucose levels, daily glucosuria levels, glycosylated hemoglobin (HbA1c) and malondialdehyde levels.. There was a significant decrease (p<0.01) in fasting blood glucose levels, mean daily blood glucose levels, daily glucosuria and HbA1c levels already after 4 months of treatment in the silymarin group. In addition, there was a significant decrease (p<0.01) in fasting insulin levels and mean exogenous insulin requirements in the treated group, while the untreated group showed a significant increase (p<0.05) in fasting insulin levels and a stabilized insulin need. These findings are consistent with the significant decrease (p<0.01) in basal and glucagon-stimulated C-peptide levels in the treated group and the significant increase in both parameters in the control group. Another interesting finding was the significant decrease (p<0.01) in malondialdehyde/levels observed in the treated group.. These results show that treatment with silymarin may reduce the lipoperoxidation of cell membranes and insulin resistance, significantly decreasing endogenous insulin overproduction and the need for exogenous insulin administration.

Topics: Aged; Antioxidants; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Glycosuria; Humans; Hyperinsulinism; Insulin; Liver Cirrhosis, Alcoholic; Male; Malondialdehyde; Middle Aged; Silymarin; Time Factors

Combination therapy with insulin and sulphonylurea has gained acceptance in management of subjects with Type 2 (non-insulin-dependent) diabetes mellitus. However, its role in management of Type 1 (insulin-dependent) diabetes mellitus remains controversial. In this study, the effect of combination therapy with insulin and glibenclamide on metabolic control, daily insulin dosage, and insulin sensitivity was assessed in subjects with Type 1 diabetes mellitus. Ten men with Type 1 diabetes mellitus participated in a randomized, double-blind, crossover, clinical trial with three treatment regimens, namely (1) insulin alone, (2) insulin and placebo, (3) insulin and glibenclamide, each lasting 3 months. Combination therapy induced: (1) reduction in daily insulin dosage; (2) more uniform blood glucose control as reflected by a lower average 24 h blood glucose level, a smaller difference between mean preprandial and 2 h postprandial blood glucose concentrations, decreased 24 h urine glucose excretion, and a decline in number of hypoglycaemic events; (3) improved insulin sensitivity as expressed by more rapid plasma glucose disappearance rate, without a significant alteration in fasting plasma glucagon and 1h postprandial serum C-peptide levels; when compared with treatment with either insulin alone or with insulin and placebo. Therefore, it is apparent that the addition of glibenclamide to insulin reduces daily insulin dosage and renders a greater uniformity to diurnal blood glucose control, most probably secondary to enhancement of insulin sensitivity.

Topics: Adult; Aged; Blood Glucose; Body Weight; C-Peptide; Cholesterol; Circadian Rhythm; Cross-Over Studies; Diabetes Mellitus, Type 1; Double-Blind Method; Drug Therapy, Combination; Glucagon; Glyburide; Glycated Hemoglobin; Glycosuria; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Male; Middle Aged; Placebos; Triglycerides

Using carefully selected relatively non-obese non insulin dependent diabetic patients, we were not able to show differences in standard measures of insulin production or insulin action between patients treated with a long acting crystalline zinc insulin, with glibenclamide, or with metformin for a six week period. All three drugs were hypoglycaemic, but a fall in basal hepatic glucose output measured by the 3H3 glucose technique was only seen in those patients who had an initial fasting plasma glucose above 12.0 mmol/l, irrespective of treatment.

Topics: Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Glucose Clamp Technique; Glyburide; Glycated Hemoglobin; Glycosuria; Humans; Insulin; Insulin Resistance; Insulin Secretion; Metabolic Clearance Rate; Metformin; Middle Aged; Radioisotope Dilution Technique; Tritium

The influence of sulfonylurea drugs in enhancing the effect of endogenous insulin is well documented. Furthermore, combination therapy with sulfonylurea and insulin is effective in the treatment of type II diabetes mellitus. Therefore, to assess the efficacy of this type of combination therapy in type I diabetes, we conducted a double-blind clinical trial with tolazamide and insulin in 15 subjects with type I diabetes. The diagnosis of type I diabetes was confirmed by previous episodes of diabetic ketoacidosis and undetectable C-peptide levels in serum samples from blood drawn from patients two hours after breakfast. During the study protocol, placebo or tolazamide was randomly added to insulin and the combination therapy was continued for three months. In the placebo group, levels of fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) did not alter significantly at the end of the study period. However, in the tolazamide group, levels of FPG and HbA1c markedly improved after administration of tolazamide (FPG levels before therapy, 10.8 +/- 0.9 mmol/L [mean +/- SEM]; after therapy, 6.7 +/- 0.4 mmol/L; HbA1c levels before therapy, 10.9% +/- 0.6%; after therapy, 9.6% +/- 0.5%). Therefore, adjuvant therapy with tolazamide and insulin may be beneficial in achieving adequate metabolic control in type I diabetes mellitus.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Double-Blind Method; Drug Therapy, Combination; Glycated Hemoglobin; Glycosuria; Humans; Insulin; Middle Aged; Random Allocation; Tolazamide

Present treatment of type II diabetes mellitus often fails to normalize post-prandial glucoses. A placebo-controlled, double-blinded design tested the effects of combined glyburide-insulin therapy over 4 months in 20 patients after achieving good control of fasting glucose with diet and intermediate insulin alone. Insulin requirements significantly decreased in both groups during the initial hospitalization when drug or placebo was added, presumably because of enforced dietary compliance. Thereafter, post-prandial glucoses worsened in the placebo group, as did hemoglobin A1c; neither of these parameters changed on the glyburide group by week 16, except for modest reduction of the 2h post-lunch glucose. Thus, while combined therapy provides little advantage beyond what can be accomplished with effective doses of intermediate insulin alone, it did reduce the need for this exogenous insulin.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Evaluation Studies as Topic; Glyburide; Glycosuria; Humans; Insulin; Male; Middle Aged

In a double-blind cross-over study we compared the effects of insulin plus glibenclamide, 5 mg twice daily, with insulin plus placebo during 8-week periods on metabolic parameters in 13 non-insulin dependent diabetic (NIDDM) patients poorly controlled with insulin alone. The combination therapy improved diabetic control as assessed by fasting blood glucose (p less than 0.001), 24-hour urinary glucose (p less than 0.01) and glycohemoglobin (HbA1) concentrations (p less than 0.05 at week 12). The effect tended to cease with time. Significantly higher C-peptide values were found during combination treatment than during insulin-placebo (p less than 0.01) and the changes in fasting C-peptide concentrations correlated positively with the changes in HbA1 concentrations (r = 0.56, p less than 0.05). There was no difference in glucagon concentrations, insulin binding to erythrocytes or insulin sensitivity between the two study periods. Neither did the combination therapy influence blood lipids significantly. The present study shows that the combination of insulin and glibenclamide may be of limited value in the treatment of NIDDM patients poorly controlled with insulin alone. However, thus far the long-term results are uncertain. In the absence of significant effects on insulin binding and insulin sensitivity, the improved diabetic control seems to be explained, at least partly, by glibenclamide-induced stimulation of insulin secretion.

Topics: Blood Glucose; Body Weight; C-Peptide; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Female; Glucagon; Glyburide; Glycated Hemoglobin; Glycosuria; Humans; Insulin; Lipids; Male; Middle Aged

Fifteen Type 2 diabetics were treated for 4-week periods with once daily (10 mg) glibenclamide, glipizide and placebo according to a double-blind cross-over protocol. Post-dose glipizide concentrations were three times higher than those of glibenclamide, due to the incomplete bioavailability of the latter. On the other hand, pre-dose drug levels were similar, as an expression of the slower absorption and/or elimination of glibenclamide. Both active treatments reduced postprandial blood glucose concentrations and 24-hour urinary glucose excretion to a similar degree, but fasting blood glucose concentrations were slightly lower during glibenclamide treatment. Both active treatments enhanced fasting and postprandial insulin and C-peptide concentrations, the C-peptide response being greater after glipizide than after glibenclamide. Plasma glucagon and GIP concentrations were not significantly affected. Insulin sensitivity was increased by glibenclamide but not by glipizide. Neither therapy affected insulin binding to erythrocytes. It appears that both glibenclamide and glipizide improved glucose metabolism by sustained stimulation of insulin secretion, which was most pronounced with glipizide. Only glibenclamide improved insulin sensitivity and was slightly more active than glipizide on fasting blood glucose levels. The differences may be consequences of the pharmacokinetics, but differences in pharmacodynamics cannot be excluded.

Topics: Aged; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus, Type 2; Double-Blind Method; Erythrocytes; Female; Gastric Inhibitory Polypeptide; Glipizide; Glucagon; Glyburide; Glycosuria; Humans; Insulin; Insulin Resistance; Kinetics; Male; Middle Aged; Random Allocation; Sulfonylurea Compounds

Thirteen patients (6 females and 7 males) who were secondary failures on oral drug therapy were randomly allocated to either 2 months of treatment with insulin + glibenclamide or insulin + placebo. Thereafter the treatment schedules of the two groups were switched over for another two months. The combination of insulin and glibenclamide was more effective in lowering the fasting blood glucose (P = 0.026) and 24 h urine glucose (P = 0.042) than the combination of insulin and placebo. The combination therapy with insulin and glibenclamide revealed higher basal (P = 0.021) and glucagon-stimulated C-peptide concentrations (P = 0.037) than therapy with insulin and placebo. However, insulin binding to erythrocytes did not differ between the two study periods. The results indicate that the addition of glibenclamide to insulin in type II diabetics poorly controlled by oral antidiabetics alone may slightly improve diabetic control. The mechanism of this action is due at least partly to sulphonylurea-induced stimulation of endogenous insulin secretion. The effectiveness of the combination treatment during long-term therapy still remains to be proven, however.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glyburide; Glycated Hemoglobin; Glycosuria; Humans; Insulin; Male; Middle Aged; Random Allocation

Twenty-four-hour metabolic profiles were performed twice in each of 15 diabetic children, once when they were receiving single daily injections of insulin (Monotard plus Actrapid) and once on a twice-daily regimen (Semitard plus Actrapid). Before the study control was optimised at home on each regimen. There were no differences in overall 24-hour diabetic control on the two regimens as measured by mean blood glucose concentration, area under the blood glucose curve, M value, and 24-hour urinary glucose excretion. Hyperglycaemia after breakfast occurred on both regimens. Significant differences were noted before breakfast, when blood glucose and ketone concentrations were lower and plasma free insulin higher on the single-injection regimen, and after supper and during the night, when blood glucose values were lower on the two-injection regimen and associated with a rise in plasma free insulin after the evening injection. Once-daily injections provided insufficient circulating insulin after the evening meal, while twice-daily injections did not last through the night. Plasma C peptide, indicating residual endogenous insulin secretion, was just detectable in two children but easily detectable in four children, whose 24-hour diabetic control was significantly better than that in the remaining 11 children.Conclusions about the superiority of one insulin regimen over another must be based on specific differences in diabetic control. Both regimens studied achieved adequate control, and though neither provided physiological control specific modifications to the regimens could help to produce more normal profiles.

Topics: Adolescent; Blood Glucose; C-Peptide; Child; Circadian Rhythm; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Food; Glycosuria; Humans; Injections, Intravenous; Insulin; Ketones; Male

The purpose of this study was to investigate how renal loss of both C-peptide and glucose during oral glucose tolerance test (OGTT) relate to and affect plasma-derived oral minimal model (OMM) indices. All individuals were recruited during family screening between August 2007 and January 2011 and underwent a 3.5-h OGTT, collecting nine plasma samples and urine during OGTT. We obtained the following three subgroups: normoglycemic, at risk, and T2D. We recruited South Asian and Caucasian families, and we report separate analyses if differences occurred. Plasma glucose, insulin, and C-peptide concentrations were analyzed as AUCs during OGTT, OMM estimate of renal C-peptide secretion, and OMM beta-cell and insulin sensitivity indices were calculated to obtain disposition indices. Post-glucose load glucose and C-peptide in urine were measured and related to plasma-based indices. Urinary glucose corresponded well with plasma glucose AUC (Cau r = 0.64, P < 0.01; SA r = 0.69, P < 0.01), S I (Cau r = -0.51, P < 0.01; SA r = -0.41, P < 0.01), Φ dynamic (Cau r = -0.41, P < 0.01; SA r = -0.57, P < 0.01), and Φ oral (Cau r = -0.61, P < 0.01; SA r = -0.73, P < 0.01). Urinary C-peptide corresponded well to plasma C-peptide AUC (Cau r = 0.45, P < 0.01; SA r = 0.33, P < 0.05) and OMM estimate of renal C-peptide secretion (r = 0.42, P < 0.01). In general, glucose excretion plasma threshold for the presence of glucose in urine was ~10-10.5 mmol L(-1) in non-T2D individuals, but not measurable in T2D individuals. Renal glucose secretion during OGTT did not influence OMM indices in general nor in T2D patients (renal clearance range 0-2.1 %, with median 0.2 % of plasma glucose AUC). C-indices of urinary glucose to detect various stages of glucose intolerance were excellent (Cau 0.83-0.98; SA 0.75-0.89). The limited role of renal glucose secretion validates the neglecting of urinary glucose secretion in kinetic models of glucose homeostasis using plasma glucose concentrations. Both C-peptide and glucose in urine collected during OGTT might be used as non-invasive measures for endogenous insulin secretion and glucose tolerance state.

Topics: Adult; Biomarkers; C-Peptide; Diabetes Mellitus, Type 2; Female; Glomerular Filtration Rate; Glucose Tolerance Test; Glycosuria; Humans; Male; Middle Aged; Models, Biological; ROC Curve

Cyclosporine A (CsA) and sirolimus (SRL) are immunosuppressive agents (IA) associated with new-onset diabetes after transplantation (NODAT). This study aims to evaluate the effects of 3-weeks of treatment with either CsA (5 mg/kg BW/day) or SRL (1 mg/kg BW/day) on insulin signaling and expression of markers involved in glucose metabolism in insulin-sensitive tissues, in Wistar rats. Although no differences were observed in fasting glucose, insulin or C-peptide levels, both treated groups displayed an impaired glucose excursion during both glucose and insulin tolerance tests. These results suggest glucose intolerance and insulin resistance. An increase in glucose-6-phosphatase protein levels (68%, p < 0.05) and in protein-tyrosine phosphatase 1B (163%, p < 0.05), a negative regulator of insulin was observed in the CsA-treated group in the liver, indicating enhanced gluconeogenesis and increased insulin resistance. On the other hand, glucokinase protein levels were decreased in the SRL group (35%, p < 0.05) compared to vehicle, suggesting a decrease in glucose disposal. SRL treatment also reduced peroxisome proliferator-activated receptor γ coactivator 1 alpha protein expression in muscle (~50%, p < 0.05), while no further protein alterations were observed in muscle and perirenal adipose tissue nor with the CsA treatment. Moreover, the phosphorylation of key proteins of the insulin signaling cascade was suppressed in the SRL group, but was unchanged by the CsA treatment. Taken together, these data suggest that CsA treatment enhances gluconeogenic factors in liver, while SRL treatment impairs insulin signaling in peripheral tissues, which can contribute to the development of insulin resistance and NODAT associated with immunosuppressive therapy.

Topics: Adipose Tissue; Animals; C-Peptide; Cyclosporine; Forkhead Transcription Factors; Gene Expression Regulation; Gluconeogenesis; Glucose Tolerance Test; Glycogen; Glycosuria; Immunosuppressive Agents; Insulin; Liver; Male; Muscle, Skeletal; Nerve Tissue Proteins; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Rats; Rats, Wistar; Signal Transduction; Sirolimus; Transcription Factors

We investigated the incidence of the slowly progressive form of type 1 diabetes (SPT1D) detected by the urine glucose-screening tests at schools in the Tokyo Metropolitan Area from 1974 to 2004. During this study period, a total of 9,242,259 school students underwent the screening program. Of them, 54 children, 19 males and 35 females, aged 11.6+/-2.4 years, were diagnosed to have SPT1D by this method. The overall incidence of SPT1D was 0.57/100,000/year, which was about one fifth of that of type 2 diabetes detected by the same method. The incidence was significantly higher in junior high school students than in primary school students (0.32 vs. 1.13/100,000/year, p<0.0001). SPT1D accounts for one third of all pediatric cases of type 1 diabetes in Japan, showing that this clinical form is not rare in Japan. There were no significant changes in the incidence of SPT1D during the study period. The incidence of type 1 diabetes in Japanese children is quite low in comparison with Caucasian populations. This incidence, regardless of the clinical form of the disease, does not seem to be influenced by environmental factors in contrast with that of type 2 diabetes.

Topics: Adolescent; C-Peptide; Child; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycosuria; Humans; Incidence; Male; Mass Screening; Schools; Tokyo

Latent autoimmune diabetes mellitus in adults (LADA) is characterized by clinical presentation as type 2 diabetes mellitus after 25 years of age, initial control achieved with oral hypoglycemic agents for at least 6 months, presence of autoantibodies and some immunogenetic features of type 1 diabetes mellitus. An 8.3 year-old girl was referred to our pediatric endocrinology department because of incidental glucosuria. She did not complain of polyuria, polydipsia, or weight loss. Her body mass index (BMI) was at the 80th percentile. Fasting glucose was 126 mg/dl, and OGTT glucose level at 120 min was 307 mg/dl. Although C-peptide levels were normal, her first phase insulin response (FIR) was lower than the 1st percentile. Anti-insulin antibody (AIA), islet cell antibody (ICA), and anti-glutamic acid decarboxylase (antiGAD) were negative. According to the clinical and laboratory findings, she was diagnosed as having type 2 diabetes mellitus. She was started with oral anti-diabetic treatment for a period of 1 year. Insulin had to be initiated for worsening of HbA1c levels. In the fourth year of follow-up, she was admitted to our hospital with diabetic ketoacidosis although she was on an intensive insulin regimen. At this time, C-peptide levels were low, antiGAD and AIA were positive with HLA DR3/DQ2 haplotype. In addition, her thyroid peroxidase antibody and endomysium antibody were found to be high at follow-up. Small intestinal biopsy revealed celiac disease. This patient may represent the first case of latent autoimmune diabetes mellitus in children (LADC) with autoimmune thyroiditis and celiac disease.

Topics: Blood Glucose; Body Mass Index; C-Peptide; Celiac Disease; Child; Diabetes Mellitus, Type 1; Female; Glycosuria; Humans; Hypoglycemic Agents; Insulin; Thyroiditis, Autoimmune

The aim of this study was to evaluate the effects of psyllium in type 2 diabetic patients.. The study included three phases: phase 1 (1 week), phase 2 (treatment, 14 g fibre/day, 6 weeks) and phase 3 (4 weeks). At the end of each phase a clinical evaluation was performed after the ingestion of a test breakfast of 1824.2 kJ (436 kcal). Measurements included concentrations of blood glucose, insulin, fructosamine, GHbA(1c), C-peptide and 24 h urinary glucose excretion. In addition, uric acid, cholesterol and several mineral and vitamin concentrations were also evaluated.. The study was performed at the Department of Pharmacology, Toxicology and Nursing at the University of León (Spain).. Twenty type 2 diabetic patients (12 men and 8 women) participated in the study with a mean age of 67.4 y for men and 66 y for women. The mean body mass index of men was 28.2 kg/m(2) and that of women 25.9 kg/m(2).. Glucose absorption decreased significantly in the presence of psyllium (12.2%); this reduction is not associated with an important change in insulin levels (5%). GHbA(1c), C-peptide and 24 h urinary glucose excretion decreased (3.8, 14.9 and 22.5%, respectively) during the treatment with fibre (no significant differences) as well as fructosamine (10.9%, significant differences). Psyllium also reduced total and LDL cholesterol (7.7 and 9.2%, respectively, significant differences), and uric acid (10%, significant difference). Minerals and vitamins did not show important changes, except sodium that increased significantly after psyllium administration.. The results obtained indicate a beneficial therapeutic effect of psyllium (Plantaben) in the metabolic control of type 2 diabetics as well as in lowering the risk of coronary heart disease. We also conclude that consumption of this fibre does not adversely affect either mineral or vitamin A and E concentrations. Finally, for a greater effectiveness, psyllium treatment should be individually evaluated.

Topics: Aged; Blood Glucose; C-Peptide; Cholesterol; Diabetes Mellitus, Type 2; Female; Fructosamine; Glycated Hemoglobin; Glycosuria; Humans; Insulin; Male; Middle Aged; Minerals; Psyllium; Time Factors; Vitamins

Hyperzincuria is a common feature in diabetic patients, which is still not understood. Based on the above consideration, the aim of the present study was to investigate the renal handling of zinc in insulin-dependent diabetes mellitus (IDDM) patients. The glomerular filtration rate, urinary zinc excretion, zinc clearance, zinc clearance/creatinine clearance ratio, zinc tubular reabsorption, glycosuria, plasma glucose, C-peptide, glucagon, and cortisol were investigated in 10 normal individuals (Group C1 and Group C2, respectively) and 10 IDDM patients (Group E1: hyperglycemic and glycosuric and Group E2: normoglycemic and aglycosuric) during placebo or venous zinc tolerance test. The results showed that urinary zinc excretion and renal zinc clearance were increased after zinc injection in normal individuals (Group C2) and IDDM patients (Groups E1 and E2) when compared with normal individuals-placebo (Group C1). However, these renal parameters were statistically more significant in the hyperglycemic and glycosuric diabetics (Group E1). Because patients in Group E1 had the lowest plasma C-peptide levels and showed a strong negative correlation between CZn++/Ccr ratio and this hormone, we suggest that in this setting insulin inhibits urinary zinc excretion.

Topics: Adult; Blood Glucose; C-Peptide; Case-Control Studies; Creatinine; Diabetes Mellitus, Type 1; Female; Glomerular Filtration Rate; Glucagon; Glycosuria; Humans; Hydrocortisone; Kidney; Kidney Tubules; Male; Zinc

Type 2 diabetes mellitus has never previously been described in UK children, although an increasing incidence in childhood is recognized in international studies. The prevalence of obesity in UK children is increasing and is a recognized risk factor for the development of diabetes. The aim of this study was to identify and characterize children with Type 2 diabetes in the West Midlands and Leicester.. Children were identified by contacting paediatricians responsible for diabetes in five hospitals. Details were collected on demographics, mode of presentation, investigations and treatment on a standard proforma.. Eight girls were identified with Type 2 diabetes, aged 9-16 years and who were of Pakistani, Indian or Arabic origin. They were all overweight (percentage weight for height 141-209%) and had a family history of diabetes in at least two generations. They presented insidiously with hyperglycaemia and glycosuria without ketosis and five were asymptomatic. Islet cell antibodies measured in seven patients were negative. Four had acanthosis nigricans which is a cutaneous marker of insulin resistance and the other four had high plasma levels of insulin and/or C peptide. These patients are distinct from those with maturity-onset diabetes of the young (MODY). All were initially managed with dietary measures, seven have been treated with oral anti-diabetic agents of whom two have subsequently required insulin.. These are the first UK case reports of Type 2 diabetes in children. Paediatricians need to be aware of the risk of Type 2 diabetes developing in childhood in high-risk ethnic groups, particularly in association with obesity and a positive family history.

Topics: Acanthosis Nigricans; Adolescent; Body Mass Index; C-Peptide; Child; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Reducing; Female; Glycosuria; Humans; Hyperglycemia; Hypoglycemic Agents; India; Insulin; Insulin Resistance; Obesity; Pakistan; Saudi Arabia; United Kingdom

The present studies were undertaken to determine whether people with type 2 diabetes are resistant to the effects of glucose as well as insulin. Diabetic and nondiabetic subjects were studied on three occasions. Hormone secretion was inhibited with somatostatin. Insulin concentrations were kept at "basal" levels (referred to as low insulin infusion) from 0 to 180 min then increased to approximately 200 pmol/l from 181 to 360 min (referred to as high insulin infusion). Glucose concentrations were clamped at either approximately 95, approximately 130, or approximately 165 mg/dl on each occasion. In the presence of basal insulin concentrations, a progressive increase in glucose from 95 to 130 to 165 mg/dl was accompanied by a comparable and progressive decrease (P = 0.001 to 0.003 by analysis of variance [ANOVA]) in endogenous glucose production (measured with [6-(3)H]glucose) and total glucose output (measured with [2-(3)H]glucose) and incorporation of 14CO2 into glucose (an index of gluconeogenesis) in both diabetic and nondiabetic subjects, indicating normal hepatic (and perhaps renal) response to glucose. In the nondiabetic subjects, an increase in glucose concentration from 95 to 130 to 165 mg/dl resulted in a progressive increase in glucose disappearance during both the low (19.9 +/- 1.8 to 23.6 +/- 1.8 to 25.4 +/- 1.6 micromol x kg(-1) x min(-1); P = 0.003 by ANOVA) and high (36.4 +/- 3.1 to 47.6 +/- 4.5 to 61.1 +/- 7.0 micromol x kg(-1) x min(-1); P = 0.001 by ANOVA) insulin infusions. In contrast, in the diabetic subjects, whereas an increase in glucose from 95 to 130 mg/dl resulted in an increase in glucose disappearance during both the low (P = 0.001) and high (P = 0.01) dose insulin infusions, a further increase in glucose concentration to 165 mg/dl had no further effect (P = 0.41 and 0.38) on disappearance at either insulin dose (low: 14.2 +/- 0.8 to 18.2 +/- 1.1 to 18.7 +/- 2.4 micromol x kg(-1) x min(-1); high: 21.0 +/- 3.2 to 33.9 +/- 6.4 to 32.5 +/- 8.0 micromol x kg(-1) x min(-1) for 95, 130, and 165 mg/dl, respectively). We conclude that whereas glucose-induced stimulation of its own uptake is abnormal in type 2 diabetes, glucose-induced suppression of endogenous glucose production and output is not. The abnormality in uptake occurs in the presence of both basal and high insulin concentrations and is evident at glucose concentrations above but not below 130 mg/dl, implying a defect in a glucose-responsive step.

Topics: Blood Glucose; C-Peptide; Carbon Dioxide; Carbon Radioisotopes; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Female; Glucagon; Gluconeogenesis; Glucose; Glucose Clamp Technique; Glycosuria; Human Growth Hormone; Humans; Insulin; Kinetics; Male; Middle Aged; Tritium

To document the incidence of IDDM in the Province of Turin (Italy) in the 8-year period 1984-91 in children (0-14 years) and young adults (15-29 years), in relation to age, sex, monthly-seasonal variability, calendar year and urban/rural area, (all newly diagnosed cases (502) were ascertained through primary and secondary data sources and completeness of ascertainment estimated with the two sample capture-recapture method (99% in childhood and 95% in young adults). The independent effect of age, sex, calendar year, and urban/rural area was estimated with a Poisson regression model. Age-specific incidence rates were 8.42/100,000 (95% CI 7.37-9.62) and 6.72/100,000 (95% CI 5.96-7.58), respectively, in the age groups 0-14 and 15-29 years. Sex differences were evident in young adults, with an almost 1.5-fold increased risk in men (8.37/100,000, 95% CI 7.21-9.71 vs 5.00/100,000, CI 4.09-6.10). Seasonal trend was evident in childhood. Predictors of incidence rates were age, place of residence and interaction between sex and age; no temporal trend was detected. No significant differences were found in the two age-groups with respect to glycaemia, glycosuria, ketonuria, and fasting C-peptide levels. In conclusion, this study shows sex differences in IDDM risk in young adults; 55% of incident cases occurring in young adults; an independent contribution of urban/rural differences to IDDM risk; no temporal trend in 1984-91; a seasonal pattern of incidence in children; no significant differences in clinical presentation between age groups.

Topics: Adolescent; Adult; Aging; Blood Glucose; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Female; Glycosuria; Humans; Infant; Italy; Ketone Bodies; Male; Risk Factors; Rural Population; Seasons; Sex Characteristics; Urban Population

Insulin availability and routine diabetes care were cross-sectionally investigated in 122 (M/F; 59/63) insulin-dependent diabetic patients aged 6-60 years with > or = 1 year duration using a structured questionnaire interview followed by a free conversation. Haemoglobin A1c, blood glucose, and serum lipids were measured in the fasting state to assess the metabolic control. Only 12% of the patients had acceptable glycaemic control (HbA1c < 7.5%). Increased age, shorter diabetes duration, and higher body mass index were associated with better metabolic control. Omission or reduction of the insulin dose was experienced by 51% of the patients due to insulin shortage. The interview data consistently indicated that insulin non-availability had induced poor compliance to therapy regimens and lack of motivation for optimum glycaemic control. Due to limited resources, most of the patients received insufficient diabetes care and education, leading to lower rates of clinic attendance (55%), and dietary non-compliance (78.5%). Elevated haemoglobin A1c was associated with higher fasting blood glucose levels (P < 0.001), serum triglycerides (P < 0.05), and urinary glucose (P < 0.001). Measurable fasting C-peptide was observed in 52.5% of the patients and was related to the age at diagnosis, and body mass index (P < 0.001 for both). There is a considerable potential to improve diabetes care and education practice, and if accessibility to insulin is simultaneously facilitated, the glycaemic control in Sudanese diabetic patients will improve.

Topics: Adolescent; Adult; Age Factors; Blood Glucose; Body Mass Index; C-Peptide; Child; Cross-Sectional Studies; Demography; Diabetes Mellitus, Type 1; Drug Administration Schedule; Fasting; Female; Glycated Hemoglobin; Glycosuria; Humans; Insulin; Lipids; Male; Middle Aged; Regression Analysis; Socioeconomic Factors; Sudan; Surveys and Questionnaires; Triglycerides

Fifteen newly diagnosed obese Type 2 diabetic subjects were treated with diet alone for 3 months with a median 1.5 kg weight loss. Each had a Continuous Infusion of Glucose with Model Assessment (CIGMA) test, at diagnosis and at 3 months, measuring insulin and C-peptide responses, and deriving mathematically modelled measures of beta-cell function and insulin sensitivity. Median fasting glucoses were 9.6 mmol l-1 at diagnosis and 8.5 mmol l-1 at 3 months (NS). Median fasting insulin was 9.3 mU l-1 at diagnosis and 11.7 mU l-1 at 3 months (NS). Median fasting C-peptide was 0.58 nmol l-1 at diagnosis and 0.64 nmol l-1 at 3 months (p < 0.05). Median achieved plasma insulin increased from 13.8 mU l-1 at diagnosis to 17 mU l-1 at 3 months (p < 0.02); median achieved plasma C-peptide increased from 0.72 nmol l-1 at diagnosis to 0.81 nmol l-1 at 3 months (p < 0.002). Modelled beta-cell function rose from median 26% at diagnosis to 37% at 3 months (p < 0.02). Modelled insulin sensitivity showed no significant change (median 0.31 at diagnosis, 0.27 at 3 months, NS). Elevation of achieved C-peptide was positively correlated with weight loss (Rs = 0.53, p < 0.05), but not with change in fasting glucose. Diet treatment of newly diagnosed Type 2 diabetes, with modest weight loss, results primarily in improvement of insulin secretory capacity, rather than insulin sensitivity.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Fasting; Fatty Acids, Nonesterified; Female; Glucose Clamp Technique; Glycosuria; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Male; Middle Aged; Time Factors

1. The objective of the present study was to investigate whether a change in insulin therapy from bovine to purified porcine insulin would result in a decreased level of insulin antibodies (IA) in type I diabetic patients and whether there would be better metabolic control. 2. Insulin antibodies were measured by ELISA. Fifteen type I diabetic patients were prospectively followed for 8 months with monthly evaluations after changing insulin therapy from bovine to purified porcine insulin. 3. Group I patients (N = 4) had IA greater than or equal to 1.5 (value obtained by dividing the ELISA absorbance of the tested serum by the absorbance of a standard serum) at the beginning of the study. For group I patients, the modification of insulin therapy caused a 57% reduction in insulin antibody levels, and this reduction was correlated with a decrease in 24-hour glycosuria (rs = 0.66, P less than 0.001) and glycated protein (rs = 0.65, P less than 0.01). Group II patients (N = 8) had IA less than 1.5 and greater than or equal to 0.3 and group III (N = 3) had IA less than 0.3. Insulin antibody levels were unchanged during the follow-up period in both group II and group III. 4. We also studied endogenous insulin secretion, measured as fasting C-peptide, and its relationships with metabolic control and insulin antibody levels. Patients with residual insulin secretion (C-peptide greater than 60 pmol/l) showed lower levels of 24-h glycosuria, glycated protein and glycated hemoglobin. Furthermore, in this group of patients a negative correlation was found between C-peptide and insulin antibody levels (rs = -0.36, P less than 0.01). 5. We conclude that insulin antibodies could be one of the factors having a detrimental effect on metabolic control.

Topics: Adolescent; Adult; Blood Glucose; Blood Proteins; C-Peptide; Child; Diabetes Mellitus, Type 1; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Glycated Hemoglobin; Glycated Serum Proteins; Glycoproteins; Glycosuria; Humans; Insulin; Insulin Antibodies; Male; Prospective Studies

Traditional dietary advice given to people with diabetes includes eliminating simple sugars (primarily sucrose) from the diet. Many people have difficulty following this recommendation. Because patients with type I (insulin-dependent) diabetes do not need overall calorie restriction, there is no caloric reason to restrict sucrose. In this study, we looked at the effect of the isocaloric substitution of a piece of chocolate cake for a baked potato in a mixed meal to determine whether this would increase the blood glucose in patients with type I diabetes. The glucose response to a cake-added meal was significantly greater than to a standard meal. The glucose response was no different between a cake-substitution meal and a standard meal. The reproducibility studies showed no difference between repeated standard meals. The urinary glucose excretion was significantly greater after a cake-added meal but was no different with the other pairs. There were no significant differences in the counterregulatory hormone responses at baseline between any of the paired studies. In conclusion, patients with type I diabetes may substitute a sucrose-containing dessert for another carbohydrate in their diet without compromising their postprandial glucose response. These data suggest that a dessert exchange may be helpful and not harmful in the management of diabetic patients. There is an inherent variability (at least 16%) in an insulin-requiring patient's response to a meal, making self-monitoring of blood glucose and adjustment of insulin doses necessary to achieve near euglycemia.

Topics: Adult; Blood Glucose; C-Peptide; Cacao; Carbohydrate Metabolism; Diabetes Mellitus, Type 1; Diet, Diabetic; Female; Glycosuria; Humans; Male; Solanum tuberosum; Sucrose

The authors investigated in 28 type 2 diabetics the effect of addition of 21 g Sinecal fibre to the normal diet on the glucose and lipid metabolism. The value of C,peptide was significantly influenced after breakfast and a single dose of Sinecal. The other investigated parameters (blood sugar on fasting and after a meal, glycosuria, glycosylated proteins, C-peptide on fasting and after a meal, triacylglycerol and cholesterol) were not influenced by a single nor by long-term intake of Sinecal. Further development of fibre preparations with better tolerance and a greater effect on the glucose metabolism is desirable.

Topics: Aged; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Dietary Fiber; Female; Glycosuria; Humans; Male; Middle Aged

The basal and total pyruvate dehydrogenase activities were assayed in circulating lymphocytes from children with juvenile diabetes at diagnosis and after five days of insulin therapy and from control subjects. In untreated diabetic children, basal and total pyruvate dehydrogenase activities were deeply decreased and both showed very similar values; whereas, in control subjects basal activity was about 30% lower than total activity. In diabetic patients treated with insulin (in vivo situation), both basal and total activity levels were equal or even higher than those of the control subjects. The incubation of lymphocytes from diabetic patients with insulin (5 microU/ml) (in vitro situation) stimulates, but less than in vivo, the basal and total pyruvate dehydrogenase activities.

Topics: Blood Glucose; C-Peptide; Child; Diabetes Mellitus, Type 1; Female; Glycosuria; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Insulin; Ketone Bodies; Lymphocytes; Male; Pyruvate Dehydrogenase Complex

Circulating insulin antibodies at birth and the degree of maternal metabolic control were measured in 68 infants of insulin-treated diabetic mothers. Their correlation with neonatal B cell function and with the clinical features of the infants was evaluated in order to better understand their influence on fetal outcome. Maternal metabolic control was assessed on the basis of blood glucose levels, glycosuria and the occurrence of hypoglycemia and/or ketonuria. All infants were clinically evaluated for gestational age, macrosomia, hypoglycemia, hyperbilirubinemia, hypocalcemia, and respiratory distress syndrome. Cord blood plasma glucose, C peptide, and IgG insulin antibodies were also measured. It was shown that poor maternal metabolic control was associated with a higher prevalence of fetal morbidity as well as with signs of B cell hyperfunction. Also the presence of circulating insulin antibodies correlated well with higher C peptide levels and with several neonatal complications. B cell hyperfunction, indicated by high C peptide levels in the infants of diabetic mothers, may possibly play a causal role in the pathogenesis of fetal morbidity. In conclusion, a good fetal outcome in insulin-treated diabetic pregnancies was associated with and may have depended upon: (1) good maternal metabolic control, and (2) absence or low levels of circulating insulin antibodies.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Fetal Blood; Glycated Hemoglobin; Glycosuria; Humans; Hypoglycemia; Immunoglobulin G; Infant, Newborn; Infant, Newborn, Diseases; Insulin; Insulin Antibodies; Islets of Langerhans; Ketone Bodies; Pregnancy; Pregnancy in Diabetics

Using the modified sensitive method of measurement of urinary C-peptide immunoreactivity (CPR) excretion, we studied whether positive correlation between residual beta-cell function and metabolic consequence is present in insulin-dependent diabetes mellitus (IDDM) or not. After urinary CPR excretions were measured for 3 days in 40 IDDM, they were divided to three groups: group A, urinary CPR excretion less than 1 microgram/day (n = 16); group B, 1-4 micrograms/day (n = 15); group C, greater than or equal to 4 micrograms/day (n = 9). All subjects were treated with intensive insulin therapy for 1-2 months, and 1) fasting blood glucose (FBS) for one week, 2) 24-hr urinary sugar excretion (US) for one week, 3) M-value for daily variation of blood glucose, and 4) hemoglobin A1 (HbA1) were measured before and after intensive insulin treatment. And, we calculated mean and standard deviation (S.D.) of FBS and US. After intensive insulin therapy, a significant difference of the S.D. of FBS was seen between group A and group B (p less than 0.01). And, a significant difference of M-value was found between group A and group B (p less than 0.05). As significant differences were observed between group A and group B, which could not be divided into two groups by conventional CPR measurement, it seems likely that metabolic stability in IDDM mainly result from minimal remaining residual beta-cell function.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Glycosuria; Humans; Insulin; Islets of Langerhans; Kidney Function Tests; Middle Aged

Increasing research into the remission phase of type I diabetes mellitus stresses the importance of a non-traumatic and reliable method for the evaluation of endogenous insulin production. We compared 24-h urinary C-peptide excretion (UCE) with plasma C-peptide values before and after stimulation with 1 mg glucagon in 24 type I diabetic children. Fasting plasma C-peptide values and stimulated plasma C-peptide values showed a linear correlation with 24 h UCE. Mean plasma C-peptide levels correlated inversely with the exogenous insulin dose. A slightly better correlation was found between the exogenous insulin dose and 24 h UCE. Control data of 24 h UCE were obtained from healthy siblings. A linear correlation with age was found up to 10 years of age above which UCE values seem to reach a plateau. This effect of age, as well as the frequency of sampling was taken into account in the derivation of 95% reference intervals for UCE. The measurement of 24 h UCE appears to be a useful parameter to assess endogenous insulin production in diabetic children, provided that age is taken into account.

Topics: C-Peptide; Child; Cohort Studies; Diabetes Mellitus, Type 1; Glucagon; Glycosuria; Humans; Insulin; Ketone Bodies; Longitudinal Studies

In most studies the distribution of peripheral lymphocyte subsets at diagnosis of type 1 diabetes has been found to be altered. Lymphocyte subpopulations were therefore studied during longitudinal changes in the glycaemic control of 11 type 1 diabetics to investigate whether poor metabolic status affects these results. To avoid any influence of the etiopathogenetic mechanisms, the patients studied had a disease duration of 10 +/- 2 (SEM) years and all but one had no residual beta-cell function. The patients were selected randomly amongst those with a long record of poor glycaemic control and at the first examination they had a mean fasting blood glucose of 15 +/- 1 mmol/l and a mean glucosuria of 67 +/- 11 g/24 h. They were then hospitalized and strictly regulated using pump treatment, resulting in a massive reduction in glucosuria (0 +/- 0 g/24 h) and fasting blood glucose (6 +/- 1 mmol/l) at a second examination a week later. Five of the patients were tested for a third time 35 +/- 4 days later and were still in very good glycaemic control. Peripheral lymphocytes were labelled with monoclonal antibodies and examined by flow cytometry (FACS). Neither CD3+ (pan) T-lymphocytes, CD4+ (helper) T-cells, CD8+ (suppressor/cytotoxic) T-cells, the relation between CD4+ and CD8+ T-cells, nor the total amount of lymphocytes, changed significantly between the first, second, and third examination. None of the results were significantly different from those of healthy controls. There was no correlation between any of the immunological and metabolic parameters. It is concluded that metabolic influence on the distribution of lymphocyte subsets is unlikely.

Topics: Adult; Antibodies, Monoclonal; Antigens, Surface; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Female; Glycosuria; Humans; Insulin; Male; T-Lymphocytes

Previous studies demonstrated that administration of insulin and oral hypoglycemic agents tends to produce weight gain in type II diabetic patients. The goal of this study was to determine the potential contribution of changes in metabolic rate and urinary glucose excretion to changes in energy balance associated with treatment with glyburide and insulin. Six obese type II diabetic patients (52-61 yr old; 123-214% of ideal weight) were fed a weight-maintaining diet of fixed composition and caloric content in a Clinical Research Center. The mean fasting plasma glucose concentrations were 10.7 +/- 1.3 (+/- SE) mmol/L before treatment, 7.9 +/- 1.4 mmol/L at the end of 2 weeks of glyburide treatment, and 5.2 +/- 0.3 mmol/L at the end of 2 weeks of insulin treatment. Urinary glucose excretion decreased from 48 +/- 19 g/day before treatment to 20 +/- 9 g/day at the end of glyburide treatment and 2 +/- 1 g/day at the end of insulin treatment. Neither treatment affected mean postabsorptive resting metabolic rate (untreated 4.86 +/- 0.50 kJ/min; glyburide-treated, 4.63 +/- 0.45 kJ/min; insulin-treated, 4.70 +/- 0.46 kJ/min) or postprandial resting metabolic rate (untreated, 5.71 +/- 0.55 kJ/min; glyburide-treated, 5.60 +/- 0.39 kJ/min; insulin-treated, 5.70 +/- 0.51 kJ/min). However, the two patients with the largest decreases in urinary glucose excretion also had decreases in energy expenditure. These data indicate that many obese type II diabetic patients could have significant weight gain from reduced energy losses alone.

Topics: Blood Glucose; Blood Urea Nitrogen; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Energy Metabolism; Epinephrine; Female; Glucagon; Glyburide; Glycosuria; Humans; Insulin; Male; Middle Aged; Norepinephrine; Obesity

In an attempt to assess day-to-day variation in glycemic control, 12 type I and 12 type II diabetic subjects were hospitalized and had plasma glucose sampled frequently on two consecutive days, during which medication, diet, and physical activity were all held constant. In type I subjects, there was no significant day-to-day correlation in overall mean plasma glucose, mean preprandial plasma glucose, mean postprandial plasma glucose, or urinary glucose excretion. In contrast, these measures were all highly correlated in type II subjects. The data suggest that individuals with type I diabetes may not be able to achieve good glycemic control simply by taking the same dose or doses of insulin each day while rigorously attempting to control diet and exercise.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycosuria; Humans; Inpatients

In a previous study a close correlation was demonstrated between metabolic clearance rates of glucose (MCR) at an insulin infusion rate of 50 mU X kg-1 hr-1 when assessed with the isoglycaemic clamp technique and the simple, concomitant infusion of insulin and glucose at a fixed rate. To determine insulin sensitivity and insulin responsiveness it is necessary to construct insulin dose response curves by measuring insulin stimulated glucose disposal at various insulin levels. The aim of the present study was to validate a simple method for constructing insulin dose response curves in 8 healthy volunteers and 12 patients with varying degrees of glucose tolerance. Insulin mediated glucose disposal, expressed as MCR, was assessed during the steady states of sequential, concomitant infusions of insulin at 50, 150 and 500 mU X kg-1 hr-1 and glucose at 33, 44 and 55 mumol X kg-1 min-1 for 150, 120 and 120 min, respectively. The results were compared with the isoglycaemic clamp technique at the same sequential insulin infusion rates for 2 hr each. A close correlation was found between the assessments of the metabolic clearance rates of glucose with either test: tau = 0.80, tau = 0.80 and tau = 0.81 at 50, 150 and 500 mU X kg-1 hr-1, respectively. The mean (+/- SEM) MCR's of glucose, assessed with sequential glucose-insulin infusions and isoglycaemic clamp technique at insulin infusion rates of 50, 150 and 500 mU X kg-1 hr-1 were in the normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Glucose; Glycosuria; Humans; Infusions, Parenteral; Insulin; Insulin Resistance; Male; Metabolic Clearance Rate; Methods; Middle Aged

The metabolic control, assessed from the mean daily glucosuria, mean daily glucosuria index based on home tests, and mean haemoglobin A1 (HbA1) concentrations during 1980, and the influence of various factors on the control were analysed in 177 diabetic children and adolescents. The mean daily glucosuria was 21% of the carbohydrates in the subscribed diet, and the mean glucosuria index 55%. The mean HbA1 was 14.0%. Boys had better metabolic control than girls. Good motivation towards treatment was associated with better metabolic control. There was a negative correlation between metabolic control and both the age of the child and the duration of diabetes. Prepubertal children were better controlled than those in puberty. Adherence to the dietary regimen was related to better control, as was the patient's endogenous insulin secretion, measured by serum C-peptide concentration. There was also an association between the season and the metabolic control, the control being better in the spring than during the other seasons. On the basis of these results male sex, a good motivation towards treatment, residual beta-cell function and adherence to the prescribed diet favor good metabolic control, while a long duration of the disease, the presence of puberty and relatively high age in childhood are factors impairing the metabolic control.

Topics: Adolescent; C-Peptide; Child; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Glycosuria; Humans; Male; Patient Compliance; Seasons

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

In prescribing a diabetic diet more attention has traditionally been paid to the amount of dietary carbohydrate than to its type or structure. We have compared the effect on blood glucose of substituting unrefined, whole foods for refined, processed foods in liberal carbohydrate diets (50-55% of dietary energy) eaten by 10 diabetic children in a randomised crossover study. All measurements were made at home. The unrefined diet used whole foods (including) dried beans) supplying 60 g/day of dietary fibre. The refined diet used processed foods supplying 20 g/day of dietary fibre. Diets were isocaloric for carbohydrate, fat, and protein. Glycaemic control was assessed by daily urine analysis for glucose, home blood glucose measurements, glycosylated haemoglobin, and by a 24-hour profile of blood and urinary glucose carried out at home after 6 weeks on each diet. Glycaemic control was significantly better on the unrefined diet. On profile days mean blood glucose levels on the unrefined and refined diets respectively were: preprandial: 5.5 and 8.4 mmol/l; postprandial 8.5 and 12.2 mmol/l. The mean 24-hour urinary glucose excretion on the unrefined diet was 9.3 g and on the refined diet was 38.0 g. Six months after the study the children were eating appreciably more dietary fibre than before (mean increase 13.6 g/day). Attention to food type and structure can improve blood glucose control in diabetic children and should provide an acceptable and more rational basis for dietary prescription than one based on carbohydrate quantity alone.

Topics: Adolescent; Blood Glucose; C-Peptide; Child; Diabetes Mellitus, Type 1; Dietary Fiber; Female; Glycosuria; Humans; Hypoglycemia; Insulin; Male; Patient Acceptance of Health Care; Patient Compliance

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diagnostic Errors; Glycosuria; Humans; Insulin; Insulin Antibodies; Male; Time Factors

Estimation of C-peptide (IRCP) can be used to measure the residual beta-cell function in insulin treated diabetics. IRCP was estimated in 46 juvenile diabetics. A significant correlation between basal IRCP-levels and duration of diabetes as well as daily insulin requirement could be shown. There was no linear correlation between glucosuria and IRCP. However, patients with IRCP > 1,0 ng/ml had significantly lower glucosuria ( p < 0,005). Endogenous residual function of the beta-cells seems to be of importance for metabolic control in diabetic children.

Topics: Adolescent; C-Peptide; Child; Diabetes Mellitus, Type 1; Female; Glycosuria; Humans; Insulin; Islets of Langerhans; Male; Mathematics; Time Factors

In a random one day study beta-cell function was evaluated in 210 insulin treated diabetics by the serum C-peptide concentration 6 min after iv injection of 1 mg of glucagon. Sixty-five patients (31%) had residual beta-cell function. As a group these patients were characterized by having a higher age at onset of diabetes (P less than 0.01), a shorter duration of disease (P less than 0.01) and by receiving a smaller dose of insulin (P less than 0.01). However, their quality of metabolic control did not differ from the patients without beta-cell function. Although the concentrations of post-stimulatory C-peptide correlated inversely with both the 24-hour glycosuria (P less than 0.01) and the fasting blood glucose concentrations (P less than 0.02), only a subgroup with C-peptide concentrations exceeding 0.30 pmol/ml showed a definitely better degree of metabolic control than those without beta-cell function. As this subgroup also received the smallest dose of insulin these observations suggest that maintenance of beta-cell function above this level facilitates good metabolic control. Evidence is presented suggesting that measurements of the 24-hour glycosuria undertaken in a diabetes clinic create a too optimistic impression of the quality of metabolic control during every day life.

Topics: Adolescent; Adult; Aged; Blood Glucose; C-Peptide; Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Female; Glycosuria; Humans; Insulin; Islets of Langerhans; Male; Middle Aged

In 35 children with long-standing diabetes mellitus, a significant correlation was found between the hemoglobin A1c (HbA1c)--and the 24-hour urinary glucose excretion. By contrast, 11 newly diagnosed diabetic children had grossly elevated HbA1c-concentrations, but no correlations could be established between the levels of HbA1c and the duration of symptoms, blood glucose, glycosuria, ketonuria and the acid--base status. However, HbA1c and C-peptide were significantly correlated. The elevated HbA1c-concentrations decreased towards normal in all of these 11 children after 2--3 months following adequate therapy. The results suggest that the determination of HbA1c may serve as a valuable metabolic control index in children with long-standing diabetes mellitus, but adds little information in newly diagnosed patients. For the individual diabetic child during the early treatment period, HbA1c may be the index of choice for adequacy of metabolic control.

Topics: Acid-Base Equilibrium; Adolescent; Blood Glucose; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Glycosuria; Hemoglobin A; Humans; Infant; Time Factors

A group of 58 diabetics, age 6-17 years and with a duration of diabetes of 3-14 years was studied in order to show whether the nature of the clinical manifestations and the treatment at the onset of the disease are related to the subsequent C-peptide production and also whether remaining C-peptide production is related to better diabetic control. The relations between a number of clinical and laboratory variables were analysed including the degree of ketosis and the insulin dose given at onset of diabetes, the incidence of postinitial remission period, the fasting C-peptide level after the remission period, the level of insulin antibodies and the actual diabetic control expressed as the degree of glucosuria in the patients' urine tests at home. Multiple regression analysis was the main method used. Postinitial remission was positively correlated to initial insulin dose and negatively correlated to duration of ketonuria at onset. C-peptide, which was found in 24.1% of the patients was positively correlated to age at onset and initial insulin dose, but negatively correlated to ketonuria at onset. Diabetic control was positively correlated to insulin dose at onset and to C-peptide level, but negatively correlated to insulin antibodies. It could further be shown that patients who had received a more vigorous treatment immediately at onset had both a higher incidence of postinitial remission and a better diabetic control. The results suggest that an early diagnosis followed by rapid normalization of the metabolism at the onset of juvenile diabetes increase the possibility of preservation of some of the endogenous insulin production, which seems to facilitate diabetic control.

Topics: Adolescent; Age Factors; C-Peptide; Child; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Glycosuria; HLA Antigens; Humans; Insulin; Insulin Antibodies; Ketone Bodies; Male; Peptides; Regression Analysis; Remission, Spontaneous; Time Factors