United Kingdom Prospective Diabetes Study (UKPDS). 13: Relative efficacy of randomly allocated diet,sulphonylurea, insulin,or metformin in patients with newly diagnosed non-insulin dependent diabetes followed for three years.

OBJECTIVE--To assess the relative efficacy of treatments for non-insulin dependent diabetes over three years from diagnosis. DESIGN--Multicentre, randomised, controlled trial allocating patients to treatment with diet alone or additional chlorpropamide, glibenclamide, insulin, or metformin (if obese) to achieve fasting plasma glucose concentrations < or = 6 mmol/l. SETTING--Outpatient diabetic clinics in 15 British hospitals. SUBJECTS--2520 subjects who, after a three month dietary run in period, had fasting plasma glucose concentrations of 6.1-14.9 mmol/l but no hyperglycaemic symptoms. MAIN OUTCOME MEASURES--Fasting plasma glucose, glycated haemoglobin, and fasting plasma insulin concentrations; body weight; compliance; and hypoglycaemia. RESULTS--Median fasting plasma glucose concentrations were significantly lower at three years in patients allocated to chlorpropamide, glibenclamide, or insulin rather than diet alone (7.0, 7.6, 7.4, and 9.0 mmol/l respectively; P < 0.001) with lower mean glycated haemoglobin values (6.8%, 6.9%, 7.0%, and 7.6%, respectively; P < 0.001). Mean body weight increased significantly with chlorpropamide, glibenclamide, and insulin but not diet (by 3.5, 4.8, 4.8, and 1.7 kg; P < 0.001). A similar pattern was seen for mean fasting plasma insulin concentration (by 0.9, 1.2, 2.4, and -0.1 mU/l; P < 0.001). In obese subjects metformin was as effective as the other drugs with no change in mean body weight and significant reduction in mean fasting plasma insulin concentration (-2.5 mU/l; P < 0.001). More hypoglycaemic episodes occurred with sulphonylurea or insulin than with diet or metformin. CONCLUSION--The drugs had similar glucose lowering efficacy, although most patients remained hyperglycaemic. Long term follow up is required to determine the risk-benefit ratio of the glycaemic improvement, side effects, changes in body weight, and plasma insulin concentration.     

Alterations of plasma opioid activity in human diabetics

Plasma opioid levels were determined in 9 obese non-diabetic subjects, their 8 age matched controls, and in 29 diabetic patients; 10 maintained on diet alone, 6 on an oral hypoglycemic agent (chlorpropamide) and 13 treated with insulin. Five age matched controls for the diabetic groups were also studied for comparison. β-endorphin and met-enkephalin levels were measured by radioimmunoassay. Enkephalin-like activity was measured by a receptor assay. Among the study groups, diabetic patients receiving insulin showed a 64% elevation of plasma β-endorphins and diabetic patients on chlorpropamide showed a 121% increase in enkephalin-like activity. There were no statistically significant differences in the plasma met-enkephalin values in the treatment groups though levels were decreased (p<0.05) in diabetics vs non-diabetics. The pathophysiological importance of these alterations remains to be elucidated.     

Serum thyroglobulin concentration in patients with diabetes mellitus

The serum thyroglobulin (Tg) concentration was measured in 97 patients with diabetes mellitus (39 males, 58 females). Hyper Tg-nemia which exceeds the normal range (1.0-26.6 ng/ml) was observed in 10 patients (3 out of 21 cases treated with diet alone, 3 out of 50 cases treated with oral hypoglycemic agents, 4 out of 26 cases treated with insulin). There was no significant correlation between concentrations of serum Tg and triiodothyronine (T3), thyroxine (T4), fasting plasma glucose (FPG), and hemoglobin A1c (HbA1c). However, a positive correlation was observed between serum concentrations of Tg and thyroid stimulating hormone (TSH). Patients with diabetes were divided into three groups according to the mode of treatment (Group I; diet alone, n = 21, Group II; oral hypoglycemic agents, n = 50, Group III; insulin, n = 26). No significant difference in the serum Tg concentration was observed among the three groups. They were also divided into two groups; normal Tg-nemia (Group A, n = 87) and hyper Tg-nemia (Group B, n = 10). There was no difference between levels of T3, T4, FPG, and HbA1c in the two groups. The serum TSH concentration measured by double antibody RIA and two site immunoradiometric assay in Group B was significantly higher than that in Group A. These results suggest that hyper Tg-nemia in patients with diabetes could be due to the increased TSH concentration which reflects latent subclinical primary hypothyroidism in them.     

Comparison of metformin and chlorpropamide in non-obese,maturity-onset diabetics uncontrolled by diet.

The clinical effectiveness of metformin was compared with that of chlorpropamide in closely similar groups of 216 non-obese patients recently diagnosed as cases of maturity-onset diabetes that could not be controlled by diet. The incidences of primary and secondary drug failures in each group and the numbers of patients satisfactorily maintained on each of the hypoglycaemic agents throughout the first year proved remarkably similar. In 61 of the successfully treated patients who were studied by crossover to the other drug and observed for a further year the mean blood glucose concentrations at the end of the year were roughly comparable, but the mean weight response was a small loss of 1.5 +/- 3.8 kg with metformin but a gain of 4.6 +/- 3.9 kg with chlorpropamide. Thus for non-obese, maturity-onset diabetics whose disease cannot be controlled by diet and who require oral treatment sulphonylureas and biguanides are equally effective, the choice depending on whether the patient is underweight and the severity of symptoms.     

Comparison of high fibre diets,basal insulin supplements,and flexible insulin treatment for non-insulin dependent (type II) diabetics poorly controlled with sulphonylureas.

OBJECTIVE--To compare high fibre diet, basal insulin supplements and a regimen of insulin four times daily in non-insulin dependent (type II) diabetic patients who were poorly controlled with sulphonylureas. DESIGN--Run in period lasting 2-3 months during which self monitoring of glucose concentration was taught, followed by six months on a high fibre diet, followed by six months'' treatment with insulin in those patients who did not respond to the high fibre diet. SETTING--Teaching hospital diabetic clinics. PATIENTS--33 patients who had had diabetes for at least two years and had haemoglobin A1 concentrations over 10% despite receiving nearly maximum doses of oral hypoglycaemic agents. No absolute indications for treatment with insulin. INTERVENTIONS--During the high fibre diet daily fibre intake was increased by a mean of 16 g (95% confidence interval 12 to 20 g.) Twenty five patients were then started on once daily insulin. After three months 14 patients were started on four injections of insulin daily. ENDPOINT--Control of diabetes (haemoglobin A1 concentration less than or equal to 10% and fasting plasma glucose concentration less than or equal to 6 mmol/l) or completion of six months on insulin treatment. MEASUREMENTS AND MAIN RESULTS-- No change in weight, diet, or concentrations of fasting glucose or haemoglobin A1 occurred during run in period. During high fibre diet there were no changes in haemoglobin A1 concentrations, but mean fasting glucose concentrations rose by 1.7 mmol/l (95% confidence interval 0.9 to 2.5, p less than 0.01). With once daily insulin mean concentrations of fasting plasma glucose fell from 12.6 to 7.6 mmol/l (p less than 0.001) and haemoglobin A1 from 14.6% to 11.2% (p less than 0.001). With insulin four times daily concentrations of haemoglobin A1 fell from 11.5% to 9.6% (p less than 0.02). Lipid concentrations were unchanged by high fibre diet. In patients receiving insulin the mean cholesterol concentrations fell from 7.1 to 6.4 mmol/l (p less than 0.0001), high density lipoprotein concentrations rose from 1.1 to 1.29 mmol/l (p less than 0.01), and triglyceride concentrations fell from 2.67 to 1.86 mmol/l (p less than 0.05). Patients taking insulin gained weight and those taking it four times daily gained an average of 4.2 kg. CONCLUSIONS--High fibre diets worsen control of diabetes in patients who are poorly controlled with oral hypoglycaemic agents. Maximum improvements in control of diabetes were achieved by taking insulin four times daily.     

Short-term and long-term effects of guar on postprandial plasma glucose, insulin and glucagon-like peptide 1 concentration in healthy rats.

Ingestion of guar gum decreases postprandial glycemia and insulinemia and improves sensitivity to insulin in diabetic patients and several animal models of diabetes. The aim of the present study was to compare the short-term and long-term effects of guar on plasma insulin and glucagon-like peptide 1 concentration in healthy rats. In the short-term experiments, the concomitant intragastric administration of glucose and guar reduced the early increment in plasma glucose, insulin and glucagon-like peptide 1 concentration otherwise induced by glucose alone. Comparable findings were made after twelve days of meal training exposing the rats to either a control or guar-enriched diet for fifteen minutes. Mean plasma glucose concentrations were lower while mean insulin concentrations were higher in the guar group than in the controls according to intragastric glucose tolerance tests conducted in overnight fasted rats maintained for 19 to 36 days on either the control or guar-enriched diet. The intestinal content of glucagon-like peptide 1 at the end of the experiments was also lower in the guar group. Changes in body weight over 62 days of observation were comparable in the control and guar rats. Thus, long-term intake of guar improves glucose tolerance and insulin response to glucose absorption, without improving insulin sensitivity, in healthy rats.     

Three months energy restricted diet does not reduce peripheral insulin resistance in newly diagnosed non insulin dependent diabetics

Sixteen newly diagnosed non insulin dependent diabetic patients were treated for 3 months with an individual energy restricted diet. The effect on weight, hyperglycaemia and insulin response to oral glucose was measured in all subjects, and in 7, peripheral insulin resistance was estimated using a hyperinsulinaemic glucose clamp at two insulin infusion rates (40 and 400 mU m-2 X min-1). After diet, fasting plasma glucose fell from 12.0 +/- 0.7 mmol/l (mean +/- SEM) to 7.4 +/- 0.5 mmol/l (P less than 0.001) and weight fell from 92.9 +/- 4.2 kg to 85.0 +/- 3.1 kg (P less than 0.001). The plasma insulin response to oral glucose was unchanged after diet therapy. Insulin induced glucose disposal (M) was also unaffected by diet at insulin infusion rates of 40 mU m-2 X min-1 (12.5 +/- 1.5 mumol X kg-1 X min-1 vs 15.7 +/- 1.6 mumol X kg-1 X min-1) and 400 mU m-2 X min-1 (49.5 +/- 2.7 mumol X kg-1 X min-1 vs 55.1 +/- 2.5 mumol X kg-1 X min-1). These results show that 3 months reduction of energy consumption with weight loss in newly diagnosed non insulin dependent diabetics improves B-cell responsiveness to glucose but has no effect on liver glucose output or on peripheral insulin action.     

Blood glucose control and glomerular capillary basement membrane thickening in experimental diabetes.

Glomerular capillary basement membrane thickness (BMT) was measured in 23 rats which had had streptozocin-induced diabetes for 14 months and in 12 age-matched controls. Diabetic rats were randomly allocated to different groups, either receiving no treatment or treated with a low carbohydrate diet or insulin, or both. Control rats were randomly allocated to a normal or low carbohydrate diet. Among the diabetic rats mean plasma glucose concentrations for the groups ranged from 27-4 mmol/l (494 mg/100 ml) in the untreated rats to 9-8 mmol/l (177 mg/100 ml) in those receiving both a low carbohydrate diet and insulin. A highly significant positive relation was found between BMT and plasma glucose concentration for individual rats. When BMT was corrected for body weight a similar relation was observed.     

Thiazolidinediones improve beta-cell function in type 2 diabetic patients

Thiazolidinediones (TZDs) improve glycemic control and insulin sensitivity in patients with type 2 diabetes mellitus (T2DM). There is growing evidence from in vivo and in vitro studies that TZDs improve pancreatic beta-cell function. The aim of this study was to determine whether TZD-induced improvement in glycemic control is associated with improved beta-cell function. We studied 11 normal glucose-tolerant and 53 T2DM subjects [age 53+/-2 yr; BMI 29.4+/-0.8 kg/m2; fasting plasma glucose (FPG) 10.3+/-0.4 mM; Hb A1c 8.2+/-0.3%]. Diabetic patients were randomized to receive placebo or TZD for 4 mo. Subjects received 1) 2-h OGTT with determination of plasma glucose, insulin, and C-peptide concentrations and 2) two-step euglycemic insulin (40 and 160 mU.m-2.min-1) clamp with [3-(3)H]glucose. T2DM patients were then randomized to receive 4 mo of treatment with pioglitazone (45 mg/day), rosiglitazone (8 mg/day), or placebo. Pioglitazone and rosiglitazone similarly improved FPG, mean plasma glucose during OGTT, Hb A1c, and insulin-mediated total body glucose disposal (Rd) and decreased mean plasma FFA during OGTT (all P<0.01, ANOVA). The insulin secretion/insulin resistance (disposition) index [DeltaISR(AUC)/Deltaglucose(AUC)/IR] was significantly improved in all TZD-treated groups: +1.8+/-0.7 (PIO+drug-na?ve diabetics), +0.7+/-0.3 (PIO+sulfonylurea-treated diabetics), and 0.7+/-0.2 (ROSI+sulfonylurea-withdrawn diabetics) vs. -0.2+/-0.3 in the two placebo groups (P<0.01, all TZDs vs. placebo, ANOVA). Improved insulin secretion correlated positively with increased body weight, fat mass, and Rd and inversely with decreased plasma glucose and FFA during the OGTT. In T2DM patients, TZD treatment leads to improved beta-cell function, which correlates strongly with improved glycemic control.     

Plasma glucose and insulin responses in growing rats fed a total parenteral nutrition diet either intravenously or intragastrically

The effect of administering either intravenously (group I) or intragastrically (group II) a glucose-amino acid total parenteral nutrition diet over a 12-day period upon plasma glucose and insulin responses was examined in adolescent rats. Infusion of the 25% glucose - 12.2% amino acid diet at a rate of 300 kCal X kg body weight-1 X 24 h-1 supported normal weight gain over the 12-day study period in both intravenously (group I) and intragastrically (group II) alimented rats. Mean plasma glucose levels rose dramatically in both groups by the end of day 1; group I had significantly higher mean plasma insulin levels. By day 3, the group I mean plasma glucose value decreased significantly while the group II mean glucose value remained virtually unchanged. Mean plasma insulin values more than doubled in both groups with the group I level still remaining significantly above the group II level. At days 6 and 12, group I mean plasma glucose levels were significantly below group II while both groups had similar plasma insulin levels. Data from this 12-day intravenous-intragastric alimentation study reveals quite different metabolic responses compared with acute (120-180 min) studies of the enteroinsular axis.     

Haemoglobin AIc concentrations after initial insulin treatment for newly discovered diabetes.

Glycosylated haemoglobins AIa+Ib and AIc were measured serially in 10 consecutive cases of newly discovered non-acidotic diabetes before and after diet and insulin treatment. The average concentration of Hb AIc was 11.4% in untreated diabetics as compared with 4.3% in healthy controls. With prolonged optimal regulation of blood glucose Hb AIc slowly decreased to a mean concentration of 5.5%. The concentration of Hb AIc was significantly correlated with the fasting blood sugar value. The findings suggest that determining Hb AIc may give valuable information on the regulation of carbohydrate metabolism in the preceding one to two months and thus become an important aid to management.     

Diabetes Mellitus: Distinguishing Between Patients Receiving Insulin and Those Requiring Insulin Therapy

Fifteen patients with maturity onset type diabetes, all of whom had received insulin for periods of one to thirty-five years, were admitted to hospital and insulin treatment was discontinued. Within 24 to 48 hours each patient was given an intravenous tolbutamide test, following which all were given either diet therapy alone or diet therapy plus oral agents. If significant hyperglycemia or ketonemia resulted, insulin therapy was reinstituted.Approximately 50 percent (8 of 15) of the patients showed improvement in fasting blood sugar levels following discontinuation of insulin. It was not possible to distinguish the insulin independent from the insulin dependent group using such criteria as age, sex, degree of overweight, insulin dosage, duration of diabetes or duration of insulin therapy. However, using the intravenous tolbutamide test it was possible to differentiate between the two groups. Those who did not require insulin responded to intravenous tolbutamide with a glucose decrease greater than 10 percent from the initial value. The insulin dependent group had either no glucose decrease or a rise in blood glucose following intravenous administration of tolbutamide.     

Insulin release from a cloned hamster B-cell line (HIT-T15). The effects of glucose, amino acids, sulphonylureas and colchicine

Insulin release from statically incubated HIT-T15 cells was maximally stimulated by glucose, L-arginine and L-leucine. L-arginine stimulated insulin release in the absence of glucose. Glucose induced insulin release was potentiated by the addition of L-leucine, L-arginine and the two in combination. Both glibenclamide and chlorpropamide stimulated insulin release from HIT-T15 cells. Glibenclamide was the more potent and equivalent in insulinotrophic action to 7.5 mmol/l glucose. Only chlorpropamide significantly potentiated glucose induced insulin release. Perifused HIT-T15 cells produced a reproducible biphasic insulin response to glucose challenge which was characterised by a pronounced and sustained first phase and a reduced second phase. The stimulation of phase I by glibenclamide alone and the inhibition of phase II of glucose induced insulin release by colchicine suggested the presence of a readily available pool of insulin granules which was not rapidly restored by insulin biosynthesis and granule margination.     

Effect of short- and long-term chlorpropamide therapy on oral glucose tolerance and erythrocyte insulin receptors in non-obese non-insulin dependent diabetes mellitus

Erythrocyte (RBC) insulin receptors and the insulin response to glucose load (oGTT) were evaluated in ten male, non-obese, non-insulin dependent diabetic patients (NIDDM) before and after 14 and 90 days of 250 mg/day of chlorpropamide administration. In addition, as a control group, twelve healthy non-obese subjects were studied. Diabetic patients with fasting plasma glucose level higher than 14 mmol/l (group A), presented a significant improvement in the incremental glucose area only after 90 days of therapy. There was an evident reduction in insulin secretion, in comparison to normals, which however increased progressively during drug administration. No alterations in insulin binding to RBC receptors were observed either before or after the use of chlorpropamide, but the normalization of the initially low number of receptors per cell (N) and an increased high affinity constant (Ke) were achieved. In group B with fasting glucose less than 14 mmol/l there was a significant reduction in plasma glucose levels during oGTT without changes in glucose areas and a significant improvement of the insulin secretion was noted only in the early samples. Except for transient alterations in N and Ke no significant changes were observed in insulin-RBC binding parameters. We conclude that the improvement in the glucose tolerance in NIDDM is associated both to a greater insulin secretion and to the correction of the alterations in receptor parameters which could be related, at least partially, to proportionate changes in reticulocyte count.     

Beneficial effects of a long-term oral L-arginine treatment added to a hypocaloric diet and exercise training program in obese, insulin-resistant type 2 diabetic patients

Because chronic L-arginine supplementation improves insulin sensitivity and endothelial function in nonobese type 2 diabetic patients, the aim of this study was to evaluate the effects of a long-term oral L-arginine therapy on adipose fat mass (FM) and muscle free-fat mass (FFM) distribution, daily glucose levels, insulin sensitivity, endothelial function, oxidative stress, and adipokine release in obese type 2 diabetic patients with insulin resistance who were treated with a combined period of hypocaloric diet and exercise training. Thirty-three type 2 diabetic patients participated in a hypocaloric diet plus an exercise training program for 21 days. Furthermore, they were divided into two groups in randomized order: the first group was also treated with L-arginine (8.3 g/day), and the second group was treated with placebo. Although in the placebo group body weight, waist circumference, daily glucose profiles, fructosamine, insulin, and homeostasis model assessment index significantly decreased, L-arginine supplementation further decreased FM (P < 0.05) and waist circumference (P < 0.0001), preserving FFM (P < 0.03), and improved mean daily glucose profiles (P < 0.0001) and fructosamine (P < 0.03). Moreover, change in area under the curve of cGMP (second messenger of nitric oxide; P < 0.001), superoxide dismutase (index of antioxidant capacity; P < 0.01), and adiponectin levels (P < 0.02) increased, whereas basal endothelin-1 levels (P < 0.01) and leptin-to-adiponectin ratio (P < 0.05) decreased in the L-arginine group. Long-term oral L-arginine treatment resulted in an additive effect compared with a diet and exercise training program alone on glucose metabolism and insulin sensitivity. Furthermore, it improved endothelial function, oxidative stress, and adipokine release in obese type 2 diabetic patients with insulin resistance.     

Zinc Supplementation Does Not Affect Glucagon Response to Intravenous Glucose and Insulin Infusion in Patients with Well-Controlled Type 2 Diabetes

Glucagon dysregulation is an essential component in the pathophysiology of type 2 diabetes. Studies in vitro and in animal models have shown that zinc co-secreted with insulin suppresses glucagon secretion. Zinc supplementation improves blood glucose control in patients with type 2 diabetes, although there is little information about how zinc supplementation may affect glucagon secretion. The objective of this study was to evaluate the effect of 1-year zinc supplementation on fasting plasma glucagon concentration and in response to intravenous glucose and insulin infusion in patients with type 2 diabetes. A cross-sectional study was performed after 1-year of intervention with 30 mg/day zinc supplementation or a placebo on 28 patients with type 2 diabetes. Demographic, anthropometric, and biochemical parameters were determined. Fasting plasma glucagon and in response to intravenous glucose and insulin infusion were evaluated. Patients of both placebo and supplemented groups presented a well control of diabetes, with mean values of fasting blood glucose and glycated hemoglobin within the therapeutic goals established by ADA. No significant differences were observed in plasma glucagon concentration, glucagon/glucose ratio or glucagon/insulin ratio fasting, after glucose or after insulin infusions between placebo and supplemented groups. No significant effects of glucose or insulin infusions were observed on plasma glucagon concentration. One-year zinc supplementation did not affect fasting plasma glucagon nor response to intravenous glucose or insulin infusion in well-controlled type 2 diabetes patients with an adequate zinc status.     

Effects of an olive oil-enriched diet on glucagon-like peptide 1 release and intestinal content, plasma insulin concentration, glucose tolerance and pancreatic insulin content in an animal model of type 2 diabetes.

In the light of a recent study conducted in normal rats, the present investigations were aimed at exploring the immediate and long-term effects of an olive oil-enriched diet (OO diet) on GLP-1 release and intestinal content, plasma insulin concentration, glucose tolerance and pancreatic insulin content in adult rats that had been injected with streptozotocin during the neonatal period (STZ rats). The OO diet, when compared to a standard diet, increased the immediate GLP-1 response in meal-trained rats, but decreased GLP-1 content in the intestinal tract after 50 days. Over 50 days, the body weight gain was lower in the rats fed the OO diet compared to standard diet. In the former, however, no improvement of glucose tolerance or insulin response during an oral glucose tolerance test was observed. Thus, a paradoxical lowering of the insulinogenic index, i. e. the paired ratio between plasma insulin and glucose concentration, was recorded during the oral glucose tolerance test in rats fed either standard or OO diet. Moreover, the insulin content of the pancreas was equally low in the STZ rats fed either standard or OO diet. These findings will be discussed in the framework of possible differences in the pathophysiology of B-cell dysfunction in most patients with type-2 diabetes and the present animal model of non-insulin-dependent diabetes.     

Recombinant glucagon-like peptide-1 (7-36 amide) lowers fasting serum glucose in a broad spectrum of patients with type 2 diabetes.

AIMS: To evaluate the safety and efficacy of various doses of recombinant glucagon-like peptide-1 (7-36) amide (rGLP-1) administered subcutaneously (s. c.) via bolus injection or continuous infusion to lower fasting serum glucose (FSG) levels in subjects with type 2 diabetes treated by diet, hypoglycemic drugs, or insulin injection. METHODS: rGLP-1 was administered s. c. to 40 type 2 diabetics currently treated by diet, sulfonylurea (SU), metformin, or insulin in a double-blind, placebo-controlled, cross-over trial; preexisting treatments were continued during the study. In the bolus injection protocol, 32 subjects (8 from each of the 4 treatment groups) received 0.0, 0.5, 1.0, and 1.5 nmol rGLP-1/kg per injection (two injections, two hours apart, beginning one hour after the evening meal) in a randomized order on separate days. In the continuous s. c. infusion protocol, 40 subjects received rGLP-1 at 0.0, 1.5, 2.5, 3.5, and 4.5 pmol/kg/min for 10-12 hours overnight starting one hour after the evening meal. Fasting bloods were taken the morning after for glucose, insulin, and glucagon measurements. RESULTS: In the diet, SU, and metformin cohorts, bolus rGLP-1 injections produced modest reductions in mean FSG levels, averaging 17.4 mg/dl (7.3-27.5; 95 % CI) at the highest dose (p < 0.001 vs. placebo). Reductions in FSG levels were greater by continuous infusion at up to 30.3 mg/dl (18.8 - 41.8; 95 % CI; p < 0.001 vs. placebo). The greatest reduction in mean FSG occurred in the SU cohort (up to 43.9 mg/dl, 24.7 - 63.1; 95 % CI; p < 0.001). rGLP-1 infusions resulted in significant increases in fasting plasma insulin and decreases in fasting plasma glucagon levels. There were no serious adverse events; GI-related symptoms were dose-related and more commonly associated with injections. CONCLUSIONS: rGLP-1 (7-36) amide dose-dependently lowered FSG in a broad spectrum of type 2 diabetics when added to their existing treatment. Subcutaneous infusion was more effective than injection, and the combination with SU was more effective than with metformin.     

A comparison of the effectiveness, tolerability and safety of high and low carbohydrate diets in women with gestational diabetes

INTRODUCTION: Nutrition therapy is an integral part of the management of gestational diabetes mellitus (GDM). Most women with GDM are treated by nutritional management alone. The goal of our study was to compare low and high carbohydrate diets in their effectiveness, safety and tolerability in women with GDM. MATERIAL AND METHODS: The study group consisted of 30 Caucasian women newly diagnosed with GDM, with a mean age of 28.7 +/- 3.7 years and pregnancy duration of 29.2 +/- 5.4 weeks. The patients were randomised into two groups: those on a low and those on a high carbohydrate diet (45% vs. 65% respectively of energy supply coming from carbohydrates). The presence of urine ketones was controlled every day. After two weeks daily glucose profiles and compliance with the recommended diets were analysed. RESULTS: Glucose concentration before implementation of the diet regimen did not differ between groups. No changes in fasting blood glucose were noticed in the group that had followed a low carbohydrate diet, although a significant decrease in glucose concentration was observed after breakfast (102 +/- 16 vs. 94 +/- 11 mg/dl), lunch (105 +/- 12 vs. 99 +/- 9 mg/dl) and dinner (112 +/- 16 vs. 103 +/- 13 mg/dl) (p < 0.05). In the high carbohydrate diet group fasting and after-breakfast glucose concentration did not change. A significant decrease in glycaemia was noticed after lunch (106 +/- 15 vs. 96 +/- 7 mg/dl) and dinner (107 +/- 12 vs. 97 +/- 7 mg/dl) (p < 0.05). Ketonuria was not observed in either group. Obstetrical outcomes did not differ between groups. CONCLUSIONS: Both high and low carbohydrate diets are effective and safe. A diet with carbohydrate limitation should be recommended to women who experience the highest glycaemia levels after breakfast.     

Fasting plasma magnesium concentrations and glucose disposal in diabetes.

Fasting plasma concentrations of magnesium were measured by neutron activation analysis in 30 non-diabetics and 87 diabetics (55 non-insulin-treated, 32 insulin treated). Plasma concentrations of magnesium were lowest in the insulin treated group (mean 0.84 (SEM 0.01) mmol/1; 2.0 (0.02) mg/100 ml), intermediate in the non-diabetics (mean 0.89 (SEM 0.01) mmol/1; 2.2 (0.02) mg/100 ml), and highest in the non-insulin-treated diabetics (mean 0.95 (SEM 0.02) mmol/1; 2.3 (0.05) mg/100 ml). In all diabetics plasma magnesium concentrations were inversely related to plasma glucose values (rs = -0.33; p less than 0.01) and in non-insulin-treated patients to plasma insulin concentrations (rs = -0.28; p less than 0.05), the former confirming previous observations. In 67 of the diabetics the KG constant for disposal rate of glucose during a standard intravenous glucose tolerance test was directly related to fasting plasma magnesium concentrations, and this relation persisted after controlling for age, sex, body mass index, type of treatment, and glucose and insulin values. This direct relation of plasma magnesium concentration with glucose disposal was unexplained by its influence on insulin secretion but was related to insulin sensitivity; hence magnesium may be an important determinant of insulin sensitivity in maturity onset diabetes.