Altering source or amount of dietary carbohydrate has acute and chronic effects on postprandial glucose and triglycerides in type 2 diabetes: Canadian trial of Carbohydrates in Diabetes (CCD).

BACKGROUND AND AIMS: Nutrition recommendations for type 2 diabetes (T2DM) are partly guided by the postprandial responses elicited by diets varying in carbohydrate (CHO). We aimed to explore whether long-term changes in postprandial responses on low-glycemic-index (GI) or low-CHO diets were due to acute or chronic effects in T2DM. METHODS AND RESULTS: Subjects with diet-alone-treated T2DM were randomly assigned to high-CHO/high-GI (H), high-CHO/low-GI (L), or low-CHO/high-monounsaturated-fat (M) diets for 12-months. At week-0 (Baseline) postprandial responses after H-meals (55% CHO, GI = 61) were measured from 0800 h to 1600 h. After 12 mo subjects were randomly assigned to H-meals or study diet meals (L, 57% CHO, GI = 50; M, 44% CHO, GI = 61). This yielded 5 groups: H diet with H-meals (HH, n = 34); L diet with H- (LH, n = 17) or L-meals (LL, n = 16); and M diet with H- (MH, n = 18) or M meals (MM, n = 19). Postprandial glucose fluctuations were lower in LL than all other groups (p < 0.001). Changes in postprandial-triglycerides differed among groups (p < 0.001). After 12 mo in HH and MM both fasting- and postprandial-triglycerides were similar to Baseline while in MH postprandial-triglycerides were significantly higher than at Baseline (p = 0.028). In LH, triglycerides were consistently (0.18-0.34 mmol/L) higher than Baseline throughout the day, while in LL the difference from Baseline varied across the day from 0.04 to 0.36 mmol/L (p < 0.001). CONCLUSION: Low-GI and low-CHO diets have both acute and chronic effects on postprandial glucose and triglycerides in T2DM subjects. Thus, the composition of the acute test-meal and the habitual diet should be considered when interpreting the nutritional implications of different postprandial responses.

Low glycaemic index diet and disposition index in type 2 diabetes (the Canadian trial of carbohydrates in diabetes): a randomised controlled trial.

AIMS/HYPOTHESIS: We recently found that oral glucose tolerance over 1 year in type 2 diabetic patients declined to a significantly lesser degree on a low-glycaemic-index than on a reduced-carbohydrate diet. Here, we examined whether that finding was associated with an improvement in disposition index, an index of beta cell function defined as the product of insulin sensitivity and insulin secretion. Since this is a report of secondary analysis on a previously published trial, the results should be considered as hypothesis-generating. METHODS: Type 2 diabetic patients treated by diet alone (n = 162) were randomised by computer to high-carbohydrate/high-glycaemic index (High-GI, n = 52), high-carbohydrate/low-glycaemic index (Low-GI, n = 56) or low-carbohydrate/high-monounsaturated-fat (Low-CHO, n = 54) diets for 1 year in a multi-centre, parallel-design clinical trial conducted at University teaching hospitals. At baseline and at 3, 6 and 12 months participants underwent 75 g OGTTs; 27 participants dropped out or were excluded. Indices of insulin sensitivity, insulin secretion and disposition index, derived from the OGTT, were compared among diets. Those assessing the outcomes were blinded to group assignment. RESULTS: Neither muscle insulin sensitivity index nor insulinogenic index differed significantly among diets. However, a significant time x diet interaction existed for disposition index (muscle insulin sensitivity index x insulinogenic index) (p = 0.036). After 3 months, disposition index tended to be higher on Low-CHO than on Low-GI diets, namely by 0.07 h(-1) (95% CI -0.04, 0.18). However, by 12 months this reversed and disposition index became higher on Low-GI than on Low-CHO, namely by 0.12 h(-1) (0.01, 0.23; p < 0.05, baseline disposition index 0.23 h(-1)). There were no important adverse effects associated with the treatments. CONCLUSIONS/INTERPRETATION: These results suggest that, in patients with type 2 diabetes on diet alone, a Low-GI diet for 1 year increases disposition index, an index of beta cell function, compared with a Low-CHO diet.

Controlled outcome evaluation of the First Step Program: a daily physical activity intervention for individuals with type II diabetes.

OBJECTIVE: To conduct a randomised trial of a physical activity (PA) intervention, The First Step Program (FSP) for adults with type II diabetes. DESIGN: A 16-week intervention study and 24-week follow-up assessment. PARTICIPANTS: A total of 47 overweight/obese, sedentary individuals (age=52.7 +/- 5.2 y; BMI=33.3 +/- 5.6 kg/m2) recruited through a diabetes education centre. PRIMARY OUTCOME: daily PA assessed by pedometer (steps/day). SECONDARY OUTCOMES: anthropometric measures (weight, BMI, waist girth, hip girth); indicators of cardiovascular health (resting heart rate and blood pressure); glycemic control (fasting glucose, insulin, HbA1c, glucose concentration 120 min postglucose load); plasma lipid status (total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides). RESULTS: Relative to the CONTROL group, FSP participants increased their PA >3000 steps/day (approximately 30 min/day) during the intervention (P<0.0001). Waist and hip girth decreased (approximately 2-3 cm), but did not differ significantly between groups. Significant changes did not emerge for any of the other variables. CONCLUSIONS: The FSP is a practical intervention that elicits an immediate and profound change in walking behaviour. Such change is an important 'first step' towards increasing the volume and/or intensity of PA necessary to improve long-term health outcomes in this largely sedentary and overweight or obese population. Relapse by 24 weeks indicates that other strategies such as booster sessions are needed to maintain lifestyle change. Further research must determine realistic and responsive health outcomes for this population that are achievable through practical, real-world programming.

Acarbose in the treatment of elderly patients with type 2 diabetes.

AIMS: To study the effect of acarbose, an alpha-glucosidase inhibitor, on glycemic control in elderly patients with type 2 diabetes. METHODS: Elderly patients with type 2 diabetes treated with diet alone were randomly treated in a double-blind fashion with placebo (n=99) or acarbose (n=93) for 12 months. RESULTS: After 12 months of therapy, there was a statistically significant difference in the change in glycated haemoglobin (HbA(1c)) (-0.6%) in the acarbose group versus placebo, as well as in the incremental post-prandial glucose values (-2.1 mmol h/l) and mean fasting plasma glucose (-0.7 mmol/l). Although there was no effect of acarbose on insulin release, there was a clear effect of acarbose to decrease relative insulin resistance (-0.8) (HOMA method). In addition, acarbose was generally well tolerated and safe in the elderly; most discontinuations were due to gastrointestinal side effects such as flatulence and diarrhea. There were no cases of hypoglycemia reported, and no clinically relevant changes in laboratory abnormalities or vital signs during the study. CONCLUSIONS: Acarbose improves the glycemic profile and insulin sensitivity in elderly patients with type 2 diabetes who are inadequately controlled on diet alone.

Development of a theory-based daily activity intervention for individuals with type 2 diabetes.

PURPOSE: This article describes a theory-driven approach to developing a physical activity intervention for sedentary individuals with type 2 diabetes. METHODS: Development of the intervention was based on 6 essential elements of program theory: problem definition, critical inputs, mediating processes, expected outcomes, extraneous factors, and implementation issues. Each element was formulated based on available literature and in collaboration with both intended service deliverers (diabetes educators) and recipients (sedentary persons with type 2 diabetes). RESULTS: Diabetes education requires a simple physical activity intervention template that is feasible, acceptable, and effective in a variety of settings. Successful programs are individualized, specific, flexible, and based on walking. Pedometers have potential as self-monitoring and feedback tools. The primary expected outcome is an increase in physical activity, specifically walking. Behavior modification and social support are critical to adoption and adherence. CONCLUSIONS: Theory-driven interventions specify what works for whom and under what conditions of delivery. The underlying theory guides the evaluation, refinement, and clinical replication of an intervention. Recruitment, delivery, and follow-up are real-world implementation issues.

Self-awareness in diabetes: using body cues, circumstances, and strategies.

PURPOSE: This research was the first phase of a study designed to develop and pilot test an educational program to increase self-awareness of salient body cues in adults with Type 1 diabetes. The purpose of this study was to identify (1) the cues, sensations, and circumstances that people with diabetes and their families associate with hypoglycemia, euglycemia, and hyperglycemia; and (2) the types of strategies that people with diabetes use to tune in to body cues and sensations. METHODS: A series of four focus group sessions were held at monthly intervals with four female participants and four family members. These sessions were audiotaped and transcribed verbatim. RESULTS: Participants described the existence of unique as well as usual body cues for hyperglycemia and hypoglycemia and the circumstances associated with these cues. Subjective and objective strategies were identified for tuning into these body cues and sensations. CONCLUSIONS: People with diabetes should be encouraged to identify their own body cues that signify different levels of glycemia because these personal cues may be different than classical textbook symptoms. Even people with hypoglycemia unawareness may recognize unique cues that replace the autonomic ones they have lost.

Day-to-day consistency in amount and source of carbohydrate intake associated with improved blood glucose control in type 1 diabetes.

OBJECTIVE: To determine if a relationship exists between blood glucose control and variability in nutrient intake from day-to-day in subjects with type 1 diabetes. METHODS: Two three-day diet records and one measurement of glycated hemoglobin (HbA1c) were obtained from 272 subjects with type 1 diabetes treated with a mixture of regular and NPH insulins before breakfast and supper and using a standardized algorithm to adjust insulin dose according to the results of self-monitoring of blood glucose two to four times daily. Day-to-day variation in nutrient intake was expressed as the coefficient of variation (CV = SDx100/mean). RESULTS: Nutrient intakes in the study population (mean +/- SD) were energy 8.35+/-2.43 MJ, fat 81+/-30 g, protein 94+/-28 g, carbohydrate 227+/-68 g, starch 126+/-38 g and dietary fiber 20+/-6 g with diet glycemic index being 84.2+/-7.4. Neither energy, nutrient intakes nor insulin dose was significantly related to HbA1c. Day-to-day variation of carbohydrate (p = 0.0097) and starch (p = 0.0016) intakes and diet glycemic index (p = 0.033) was positively related to HbA1c, and the associations remained significant when adjusted for age, sex, duration of diabetes and BMI. Day-to-day variation in energy, protein or fat intakes was not related to HbA1c. CONCLUSIONS: Consistency in the amount and source of carbohydrate intake from day-to-day is associated with improved blood glucose control in people with type 1 diabetes, a result which supports continued educational efforts to achieve adherence to a diabetes diet plan. This conclusion may not apply to people on intensified insulin therapy who adjust their insulin dose based on their actual carbohydrate intake at each meal.

The effect of valsartan and captopril on lipid parameters in patients with type II diabetes mellitus and nephropathy.

The study compared valsartan 80 mg or 160 mg o.d. with captopril 25 mg t.i.d. or placebo on plasma lipids in normotensive and treated hypertensive patients with type II diabetes and microalbuminuria. One hundred and twenty-two adult outpatients were randomised to receive either valsartan 80 mg or 160 mg, captopril 25 mg or placebo for 360 days. Changes from baseline to endpoint in plasma lipid parameters were measured. The primary criterion for tolerability was the incidence of adverse events. All treatment groups showed minor changes in lipid parameters. Triglyceride increased by 2.7% (valsartan 160 mg) to 9.1% (placebo). Total cholesterol decreased under valsartan 80 mg, while other groups showed increases of up to 0.031 mmol/l. Decreases in total cholesterol (p = 0.018), apolipoprotein B (p = 0.042) and apolipoprotein A1 (p = 0.025), were significant for the comparison of 80 mg valsartan and captopril. Valsartan 80 mg or 160 mg o.d. does not cause deleterious changes in the diabetic lipid profile and, unlike captopril, is not associated with dry cough.

No relationship between carbohydrate intake and effect of acarbose on HbA1c or gastrointestinal symptoms in type 2 diabetic subjects consuming 30-60% of energy from carbohydrate.

OBJECTIVE: To determine the relationship between carbohydrate intake and the effect of acarbose on HbA1c in subjects with type 2 diabetes treated with acarbose alone, acarbose plus sulfonylurea, acarbose plus metformin, or acarbose plus insulin. RESEARCH DESIGN AND METHODS: We conducted a double-blind randomized placebo-controlled study in which subjects with diabetes in four treatment strata (77 on diet alone, 83 treated with metformin, 103 treated with sulfonylurea, and 91 treated with insulin) were randomized to treatment with placebo or acarbose for 12 months. Before randomization, and 3, 6, 9, and 12 months after randomization, fasting blood was obtained for HbA1c, and 3-day diet records were collected. Subjects who completed at least 6 months of acarbose therapy and provided at least three 3-day diet records were included. RESULTS: In the 114 subjects included in this analysis, carbohydrate intake varied from approximately 30-60% of energy There was no significant relationship between carbohydrate intake and change in HbA1c in any of the four treatment strata (diet: n=26, r=0.35, P=0.076; metformin: n=27, r=0.26, P=0.19; sulfonylurea: n=35, r=0.24, P=0.16; insulin: n=25, r=-0.27, P=0.19). In the 80 subjects consuming <50% of energy from carbohydrate, the fall in HbA1c (7.83 +/-0.17% at baseline to 6.72+/-0.13% on acarbose, P < 0.001) was no different from that of the 34 subjects consuming >50% of energy from carbohydrate (7.55+/-0.25% at baseline to 6.66+/-0.23% on acarbose, P < 0.001). There was no difference in carbohydrate intake between those who dropped out of the study because of gastrointestinal side effects and those who did not, and there was no relationship between severity of symptoms and the composition of the diet. CONCLUSIONS: In subjects with type 2 diabetes consuming 30-60% of energy from carbohydrate, the effect of acarbose on HbA1c and gastrointestinal symptoms was not related to carbohydrate intake. Because most people consume at least 30% of energy from carbohydrate, we conclude that no special diet is needed for acarbose to be effective in improving blood glucose control in the treatment of type 2 diabetes.

Prevalence and epidemiology of toenail onychomycosis in diabetic subjects: a multicentre survey.

The number of individuals diagnosed with diabetes mellitus is increasing. The diabetic may present with complications involving all systems of the body. While onychomycosis is often observed in diabetics, there have been no large studies on the prevalence of the condition in this patient group. We examined the prevalence of onychomycosis in diabetics attending diabetes and dermatology clinics in London, Ontario, Canada and Boston, MA, U.S.A. Diabetic subjects seen in dermatology offices were for unrelated dermatoses; those referred specifically for the management of onychomycosis were excluded from the sample. A total of 550 diabetic subjects was evaluated (283 males and 267 females), age 56.1 +/- 0.7 years (mean +/- SEM). Patients with type I diabetes constituted 34% of the sample. The racial origin was: 531 Caucasians, 17 Asians, one African-American and one American-Indian. Abnormal-appearing nails and mycological evidence of onychomycosis (mostly due to dermatophytes) were present in 253 (46%) and 144 (26%), respectively, of 550 subjects. The development of onychomycosis was significantly correlated with age (P < 0.0001) and male gender (P < 0.0001). Males were 2.99 times more likely to have onychomycosis compared with females (95% confidence interval, CI 1.94-4 61). After controlling for age and sex, the risk odds ratio for diabetic subjects to have toenail onychomycosis was 2.77 times compared with normal individuals (95% CI 2.15-3.57). After controlling for age and sex, a stepwise logistic regression demonstrated that significant predictors for onychomycosis included a family history of onychomycosis (P = 0.0001), concurrent intake of immunosuppressive therapy (P = 0.035) and peripheral vascular disease (P = 0.023). Toenail onychomycosis was present in 26% of the sample and is projected to affect approximately one-third of subjects with diabetes. Predisposing factors include increasing age, male gender, family history of onychomycosis, concurrent intake of immunosuppressive agents and peripheral vascular disease.

Small weight loss on long-term acarbose therapy with no change in dietary pattern or nutrient intake of individuals with non-insulin-dependent diabetes.

OBJECTIVES: To see if the long-term treatment of non-insulin dependent diabetes (NIDDM) with the alpha-glucosidase inhibitor acarbose affects food intake and body weight. DESIGN: Randomized, double-blind, placebo-controlled, parallel design clinical trial of 12 months duration. SUBJECTS: Subjects with NIDDM in four treatment strata: 77 on diet alone, 83 also treated with metformin, 103 also treated with sulfonylurea and 91 also treated with insulin. MEASUREMENTS: Two 3 day diet records were obtained before randomization to acarbose or placebo therapy, and additional 3 day diet records were obtained at 3, 6, 9 and 12 months after randomization. Body weight was also measured at these times. RESULTS: Of the 354 subjects randomized, 279 (79%) completed at least 9 months of therapy and, of these, 263 (94%) provided at least one diet record during the baseline period and two diet records during the treatment period. After one year, subjects on acarbose had lost 0.46 +/- 0.28 kg, which differed significantly from the 0.33 +/- 0.25 kg weight gain on placebo (P = 0.027). The difference in weight change between acarbose and placebo did not differ significantly in the different treatment strata. Being in the study had significant effects on diet, including a reduction in energy intake from 1760-1700 Kcal/d (P < 0.05), a reduction in simple sugars intake from 18.5-17.4% of energy (P < 0.001), and reductions in the number of different foods consumed (33-30, P < 0.001) and the number of meals eaten per day (4.7-4.3, P < 0.001). However, compared to placebo treatment, acarbose had no effect on energy intake, nutrient intakes, or dietary patterns. CONCLUSIONS: In subjects with NIDDM on weight-maintaining diets, long-term acarbose therapy results in a small weight loss, but has no effect on energy or nutrient intakes. The weight loss induced by acarbose may be due partly to reduced doses of concomitant oral agents and insulin and partly to energy loss due to increased colonic fermentation.

Metabolic response of forearm muscle to graded exercise in type II diabetes mellitus: effect of endurance training.

In this study, 31P nuclear magnetic resonance spectroscopy was used to monitor muscle metabolism in Type II diabetic subjects (n = 10) during an incremental exercise test. Also the exercise responses of diabetic subjects (n = 4) following submaximal endurance training were assessed and compared to healthy controls (n = 5). Responses to incremental exercise in the diabetic subjects were consistent over time despite minor fluctuations in metabolic control. In the diabetic and control groups, after 12 weeks of training the forearm flexor muscles, power output at the intracellular threshold of acidosis (IT) increased (p < .01) similarly: T0 versus T12: 0.90 +/- 0.09 versus 1.20 +/- 0.13 and 1.03 +/- 0.07 versus 1.22 +/- 0.10 W, respectively. Minimum intracellular pH reached at peak exercise was unchanged after training. The control group, however, became more acidic versus the diabetic group (p < .05) in response to progressive exercise. This difference was maintained over time. Endurance training elicited similar adaptations in forearm muscles of Type II diabetic and control subjects, although there were differences between the two groups in intracellular pH during exercise.

Clinical experience with acarbose: results of a Canadian multicentre study.

Current therapeutic options for the treatment of non-insulin-dependent diabetes mellitus (NIDDM) focus on regimens that primarily lower fasting blood glucose concentrations. In several short-term studies, the alpha-glucosidase inhibitor, acarbose, has been reported to significantly lower post-prandial plasma glucose levels as well as HbA1c. The primary objective of this present study was to assess the long-term efficacy of adjunctive acarbose therapy to improve metabolic control. Over a 1-y period, acarbose or placebo was administered to 4 groups of patients: those managed by diet only, diet and sulfonylurea, diet and biguanide, and diet and insulin. In all treatment groups, the addition of acarbose resulted in significant reductions in postprandial blood glucose levels. Additionally, HbA1C was significantly lower after 12 months of acarbose therapy, compared with placebo, in all groups except the diet and insulin group. The addition of acarbose consequently expands the armamentarium available to clinicians for the optimization of glycemic control in patients with NIDDM.

One-year acarbose treatment raises fasting serum acetate in diabetic patients.

alpha-Glucosidase inhibitors such as acarbose improve blood glucose control in diabetes by delaying or reducing carbohydrate absorption. The fermentation of malabsorbed carbohydrate in the colon is associated with the production of gas, leading to flatulence, and short chain fatty acids such as acetate, which may have systemic effects. To see if acarbose raised fasting serum acetate in diabetic patients, we studied 85 subjects selected from the 267 who had completed a 1-year, double-blind, placebo-controlled, parallel design study of the effects of acarbose in the treatment of diabetes. At baseline, there was no significant difference between the 44 subjects subsequently randomized to placebo and the 41 randomized to acarbose, respectively, in fasting serum acetate (80 +/- 5 vs 71 +/- 4 mumoll-1) or glycosylated haemoglobin (HbA1C; 7.2 +/- 0.3 vs 7.4 +/- 0.3%). Compared to placebo, acarbose treatment significantly increased fasting serum acetate by 11 +/- 4 vs 2 +/- 3 mumoll-1 (p < 0.02) and reduced HbA1C by -0.59 +/- 0.16 vs -0.13 +/- 0.20% (p < 0.02). Acarbose treatment had no significant effect on serum cholesterol or non-esterified fatty acids, but was associated with a significant increase in flatulence. There was no relationship between changes in serum acetate and changes in HbA1C, serum cholesterol or symptoms. We conclude, in subjects with diabetes who tolerate therapy for a 1-year period, that acarbose treatment increases serum acetate. The magnitude of change in acetate was unrelated to side-effects or changes in blood glucose control or serum lipids.

The efficacy of acarbose in the treatment of patients with non-insulin-dependent diabetes mellitus. A multicenter controlled clinical trial.

OBJECTIVE: To evaluate the long-term efficacy of acarbose, an alpha-glucosidase inhibitor, in improving glycemic control in patients with non-insulin-dependent diabetes mellitus. DESIGN: A 1-year, multicenter, randomized, double-blind, placebo-controlled study. SETTING: Seven university-affiliated, community-based, tertiary care diabetes clinics. PATIENTS: 354 patients with non-insulin-dependent diabetes mellitus were recruited; 77 were being treated with diet alone, 83 with diet and metformin, 103 with diet and sulfonylurea, and 91 with diet and insulin. Patients in each treatment group were randomly assigned to either acarbose or placebo for 1 year. Eighty-seven percent of patients receiving acarbose and 92% of those receiving placebo were included in the efficacy analysis (n = 316). MEASUREMENTS: At baseline and at 3-month intervals, levels of hemoglobin A1c (HbA1c), fasting and postprandial plasma glucose, fasting and postprandial serum C-peptide, and fasting serum lipids were measured. RESULTS: Compared with placebo, acarbose treatment caused a significant decrease in the mean postprandial plasma glucose peak (90 minutes) in all four groups (19.0 +/- 0.4 mmol/L to 15.5 +/- 0.4 mmol/L; P < 0.001). Analysis of the postprandial plasma glucose incremental area under the curve showed that the change from baseline to the end of the treatment period differed for placebo and acarbose recipients by 4.73 mmol.h/L in the diet alone group (P < 0.001), 2.06 mmol.h/L in the metformin group (P = 0.01), 2.65 mmol.h/L in the sulfonylurea group (P < 0.001), and 3.13 mmol.h/L in the insulin group (P = 0.001). Corresponding decreases in HbA1c levels occurred; these were 0.9% in the diet alone group (P = 0.005), 0.8% in the metformin group (P = 0.011), 0.9% in the sulfonylurea group (P = 0.002), and 0.4% in the insulin group (P = 0.077). Acarbose did not significantly affect mean serum C-peptide or mean serum lipid levels. CONCLUSIONS: Acarbose improved long-term glycemic control in patients with non-insulin-dependent diabetes mellitus regardless of concomitant antidiabetic medication.

Determinants of diet glycemic index calculated retrospectively from diet records of 342 individuals with non-insulin-dependent diabetes mellitus.

Controlled trials have shown that a diet with a low glycemic index improves blood glucose and lipid control in patients with diabetes. To study the distribution and determinants of diet glycemic index, we obtained two 3-d diet records from 342 free-living subjects with non-insulin-dependent diabetes. Mean +/- SD 24-h intakes were as follows: energy, 7170 +/- 1890 kJ; fat, 33.6 +/- 6.5% of energy; protein, 20.1 +/- 3.2% of energy; available carbohydrate, 45.3 +/- 7.2% of energy; and dietary fiber, 17.2 +/- 6.4 g. Diet glycemic index values (85.4 +/- 4.55, range, 70-97.8) were normally distributed. Diet glycemic index was inversely associated with intake of simple sugars, whether expressed in grams (r = -0.426), percent of energy (r = -0.446), or percent of carbohydrate (r = -0.453, P < 0.001). By step-wise-multiple-linear regression, grams carbohydrate and percent protein were also independently related to diet glycemic index. Differences in diet glycemic index between men and women, and between subjects on different types of diabetes therapy were explained by differences in intake of simple sugars.

Endocrine-metabolic function in remission-phase IDDM during administration of cyclosporine.

We have studied the endocrine-metabolic status of patients in non-insulin-receiving (NIR) remission of insulin-dependent diabetes mellitus (IDDM) within 6-60 mo of diagnosis during administration of cyclosporine, in comparison with nondiabetic subjects. IDDM patients in NIR remission were recognized when target glycemic control (plasma glucose and mean capillary blood glucose levels less than 7.8 mM before meals) was maintained without administration of insulin for at least 2 wk. In so-called isoglycemic tests, 50 g glucose was administered orally, and the glycemic curve was simulated in a subsequent study by programmed intravenous infusion of glucose. Under these conditions, the subjects with diabetes exhibited obvious glucose intolerance: acute beta-cell responses to intravenous glucose were virtually absent but significant, although subnormal responses were present after oral glucose. The responses of plasma immunoreactive gastric inhibitory polypeptide to oral glucose were normal. After bolus intravenous injections of glucose, the patients with diabetes again exhibited glucose intolerance; acute responses of immunoreactive insulin (IRI) and C-peptide were present, although grossly obtunded. On intravenous infusion of arginine (30 g in 30 min), the patients with diabetes showed substantial but subnormal increases in plasma IRI and C-peptide. Intravenous infusion of arginine elicited increments of plasma immunoreactive glucagon (IRGI) in both groups, and this response was slightly exaggerated in the patients with diabetes. On ingestion of a standard mixed meal (Sustacal) delivering 600 cal, there was a modest but significantly greater increase in plasma glucose levels in the diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic effects of continuous subcutaneous insulin infusion: evidence that a rise and fall of portal vein insulin concentration with each major meal facilitates post-absorptive glycemic control.

Eighteen lean adult volunteers with insulin-requiring diabetes mellitus attempted to achieve normoglycemia using continuous subcutaneous insulin infusion (CSII) or conventional insulin therapy (CIT) in a randomized crossover trial of 68 +/- 2.5 weeks (mean +/- SEM) duration. As reported (Diabetes Care 8: 447-55, 1985) the group with absent to low beta-cell function (C-peptide negative, n = 11) attained mean post-absorptive normoglycemia only during CSII vs CIT (p less than 0.05). Only following CSII was this without change in post-absorptive serum triglyceride concentrations (-4 +/- 5.6 vs 12 +/- 4.7 mg/dl; -0.04 +/- 0.6 vs 0.14 +/- 0.05 mM, p less than 0.05) or body weight (0.01 +/- 0.02 vs 0.05 +/- 0.01 kg/week, p less than 0.05). In the group with glucagon stimulated serum C-peptide 100-400 pmol/L (C-peptide positive) responses to CSII or CIT were equal. As total daily insulin dosage (0.05 +/- 0.04 U/kg/day) was the same under all conditions, to explain the efficacy of CSII, glucoregulatory hormone responses were examined. Pre- and post-test breakfast serum free immunoreactive insulin and plasma glucagon concentrations were essentially unaffected by C-peptide or treatment status. Erythrocyte 125I-insulin binding was decreased in the C-peptide negative group only during CSII (8.6 +/- 0.5 vs 10.1 +/- 0.7%, p less than 0.005); C-peptide positive group receptor binding was consistently low (8.2 +/- 0.8, 8.4 +/- 0.9%). During CIT using intermediate-acting insulin post-lunch peripheral venous insulin failed to rise (p less than 0.05), but in the C-peptide positive group, on the basis of C-peptide responses to breakfast an undetected rise and fall of portal venous insulin was assumed to coincide with each meal. Thus, only during CIT in the C-peptide negative group, which received on average 6.4/wk/subject fewer pre-meal regular insulin boluses (p less than 0.01), was the frequency of meal-related change in portal insulinemia decreased. Consistent meal-related fluctuations in portal insulinemia inherent in CSII hepatocytes sensitized by a post-receptor mechanism to the suppressive effects of insulin on glucose output and thus were indirectly responsible for the observed improvement in glycemic control and lipid metabolism in the C-peptide negative group.

Effects of cyclosporine in recent-onset juvenile type 1 diabetes: impact of age and duration of disease.

Administration of cyclosporine resulted in reduced insulin requirements and improved glycemic control in patients with insulin-dependent diabetes mellitus of recent onset, but the drug was less effective in young children. Renal toxic effects and other problems related to therapy resolved after discontinuation of the drug. Sustained remission seemed dependent on continued administration of cyclosporine. Although short-term control of diabetes may be achieved in some patients, more studies are needed to determine whether cyclosporine can be given safely as maintenance therapy to maintain glycemic control and prevent the long-term consequences of the disease.