Correction of hyperglycaemia reduces insulin resistance and serum soluble E-selectin levels in patients with Type 2 diabetes mellitus.

AIMS: To investigate the effects of glycaemic control on insulin sensitivity and serum concentrations of soluble vascular cell adhesion molecule (sVCAM)-1 and E-selectin (sE-selectin) in patients with Type 2 diabetes mellitus. To examine whether reductions in serum adhesion molecule levels correlate with improvement in insulin resistance. METHODS: A total of 54 patients with Type 2 diabetes were treated for 4 weeks with either diet alone, sulphonylurea or insulin. Fasting glucose, insulin sensitivity, lipids, sVCAM-1, and sE-selectin levels were measured before and after treatment. RESULTS: All treatment modalities successfully corrected hyperglycemia. Reductions in blood glucose levels resulted in improvement in insulin sensitivity (diet KITT 2.40 +/- 0.26-3.09 +/- 0.36, P < 0.01; sulphonylurea 2.24 +/- 0.16-2.94 +/- 0.18, P < 0.01; insulin 1.68 +/- 0.27-2.16 +/- 0.22%/min, P < 0.05), and decrease in sE-selectin levels (diet 88.4 +/- 14.9-66.2 +/- 10.8, P < 0.05; sulphonylurea 85.1 +/- 11.6-59.8 +/- 7.8, P < 0.01; insulin 84.4 +/- 8.7-66.8 +/- 7.4 ng/ml, P < 0.01), but no change in sVCAM-1 levels. There was a significant correlation between the degree of decrease in sE-selectin levels and improvement in insulin sensitivity (r = -0.38, P < 0.01). CONCLUSIONS: Correction of hyperglycaemia, independent of treatment modality, resulted in improvement of insulin resistance and decrease in sE-selectin levels. These changes might, in part, contribute to reduce the risk of diabetic microvascular and macrovascular complications in patients with Type 2 diabetes mellitus.     

Dietary fat content modifies liver fat in overweight nondiabetic subjects

BACKGROUND: Fat accumulation in the liver has been shown to be closely correlated with hepatic insulin resistance and features of insulin resistance, even independent of body weight. The reason for interindividual variation in liver fat content is unknown. Cross-sectional data suggest that dietary fat content may influence liver fat, but this possibility has not been directly tested in humans. DESIGN AND METHODS: Liver fat (proton spectroscopy), intraabdominal and sc fat (magnetic resonance imaging), and markers of insulin sensitivity (insulin, free fatty acids, and lipids) were determined in 10 normal, obese women (age, 43 +/- 5 yr, mean +/- sd; body mass index, 33 +/- 4 kg/m2; range, 27-38 kg/m2) at baseline and after two 2-wk isocaloric periods containing either 16% (low-fat diet) or 56% (high-fat diet) of total energy as fat. RESULTS: Liver fat at baseline averaged 10 +/- 7%. It decreased by 20 +/- 9% during the low-fat diet and increased by 35 +/- 21% during the high-fat diet (P = 0.014 for liver fat after low- vs. high-fat diets; P = 0.042 for change in liver fat by the low- vs. high-fat diet). Fasting serum insulin averaged 70 +/- 41 pmol/liter at baseline. It decreased to 60 +/- 24 pmol/liter during the low-fat diet (P = 0.007 vs. before low-fat diet) and increased to 81 +/- 44 pmol/liter during the high-fat diet (P = 0.040 vs. before high-fat diet; P = 0.005 for change in serum insulin during low- vs. high-fat diet). Serum lipids, free fatty acids, and intraabdominal and sc fat masses were unchanged. CONCLUSION: These data suggest that the amount of dietary fat influences liver fat content.     

Comparison of a high-carbohydrate and a high-monounsaturated fat, olive oil-rich diet on the susceptibility of LDL to oxidative modification in subjects with Type 2 diabetes mellitus.

AIMS: To compare the effects of a high-carbohydrate (CHO) diet and a high-monounsaturated fatty acid (MUFA) diet on LDL oxidative resistance in free-living individuals with Type 2 diabetes mellitus. METHODS: Twenty-two men and women out-patients with Type 2 diabetes, with mean age 61 years and in fair metabolic control (HbA1c<8.0%), were enrolled at a university hospital lipid clinic in a randomized, crossover feeding trial comparing two isocaloric diets for 6 weeks each: CHO (fat, 28% energy) and MUFA (fat, 40% energy) based on virgin olive oil. Outcome measurements were changes in LDL susceptibility to oxidation, body weight, glycaemic control, and lipoprotein profiles. RESULTS: Planned and observed diets were well matched. Participants preferred the MUFA diet over the CHO diet. The lag time of conjugated diene formation during Cu2+-induced LDL oxidation was similar after the CHO and MUFA diets (36.4 +/- 12.2 min and 36.0 +/- 13.7 min, respectively). Body weight, glycaemic control, total triglycerides, and total, LDL- and HDL-cholesterol levels also were similar after the two diets. Compared with the CHO diet, the MUFA diet lowered VLDL-cholesterol by 35% (P=0.023) and VLDL triglyceride by 16% (P=0.016). CONCLUSIONS: Natural food-based high-CHO and high-MUFA diets have similar effects on LDL oxidative resistance and metabolic control in subjects with Type 2 diabetes. A MUFA diet is a good alternative to high-CHO diets for nutrition therapy of diabetes because it also has a beneficial effect on the lipid profile and superior patient acceptance.     

The effects of a low-fat, plant-based dietary intervention on body weight, metabolism, and insulin sensitivity

PURPOSE: This study investigated the effect of a low-fat, plant-based diet on body weight, metabolism, and insulin sensitivity, while controlling for exercise in free-living individuals. SUBJECTS AND METHODS: In an outpatient setting, 64 overweight, postmenopausal women were randomly assigned to a low-fat, vegan diet or a control diet based on National Cholesterol Education Program guidelines, without energy intake limits, and were asked to maintain exercise unchanged. Dietary intake, body weight and composition, resting metabolic rate, thermic effect of food, and insulin sensitivity were measured at baseline and 14 weeks. RESULTS: Mean +/- standard deviation intervention-group body weight decreased 5.8 +/- 3.2 kg, compared with 3.8 +/- 2.8 kg in the control group (P = .012). In a regression model of predictors of weight change, including diet group and changes in energy intake, thermic effect of food, resting metabolic rate, and reported energy expenditure, significant effects were found for diet group (P < .05), thermic effect of food (P < .05), and resting metabolic rate (P < .001). An index of insulin sensitivity increased from 4.6 +/- 2.9 to 5.7 +/- 3.9 (P = .017) in the intervention group, but the difference between groups was not significant (P = .17). CONCLUSION: Adoption of a low-fat, vegan diet was associated with significant weight loss in overweight postmenopausal women, despite the absence of prescribed limits on portion size or energy intake.     

Tumour necrosis factor-alpha plasma levels in elderly patients with Type 2 diabetes mellitus-observations over 2 years.

AIMS: The cytokine tumour necrosis factor-alpha (TNF-alpha) is involved in the development of obesity-linked insulin resistance. TNF-alpha plasma levels rise with increasing age and might thus also be related to metabolic control in Type 2 diabetes mellitus. We have studied the relationship of TNF-alpha plasma levels to glycaemic control in elderly patients with Type 2 diabetes over 2 years. METHODS: Clinical and laboratory data of 53 patients (26 women, 27 men) with Type 2 diabetes (mean age 71.6 +/- 5.6 years) were regularly evaluated over 2 years, and the relationship to anti-diabetic treatment regimens analysed. TNF-alpha plasma level was measured by a solid-phase enzyme amplified sensitivity immunoassay. RESULTS: TNF-alpha plasma levels increased significantly from 16.2 +/- 9.6 pg/ml at baseline to 28.0 +/- 13.8 pg/ml after 2 years (P = 0.028). HbA1c values also increased from 6.4 +/- 1.2% to 7.7 +/- 1.6% (P = 0.046). Mean body mass index of the patients remained almost constant, while a moderate increase in the percentage of body fat (34.5 +/- 7.0% to 35.3 +/- 6.9%; P= 0.061) and in waist-hip ratio was observed (0.86 +/- 0.04 to 0.88 +/- 0.04; P= 0.052). After adjustment for covariates multivariate analysis demonstrated that TNF-alpha plasma levels are positively related to the HbA1c values of the whole study population at the baseline control and after 2 years. TNF-alpha also revealed a positive correlation to the percentage of body fat. CONCLUSIONS: In elderly patients with Type 2 diabetes TNF-alpha plasma levels revealed a continuous increase during an observation period of 2 years. This increase in TNF-alpha plasma levels might add another aspect to the worsening of glycaemic control in the progression of Type 2 diabetes.     

Consumption of a controlled low-fat diet containing olestra for 9 months improves health risk factors in conjunction with weight loss in obese men: the Ole' Study

OBJECTIVE: To compare the effects of a standard American diet, a traditional low-fat diet, and a low-fat diet containing the fat substitute olestra on risk factors for heart disease and diabetes. DESIGN: A 9-month, double-blind, randomized, parallel-arm, feeding study comparing three diets: (1). control (33% fat), (2). fat-reduced (FR; 25% fat), and (3). fat-substituted (FS) where olestra replaced 1/3 of dietary fat (33% lipid and 25% digestible fat). Subjects were allowed to adjust their total energy intake as desired, allowing weight to fluctuate. SUBJECTS: A total of 37 healthy, obese men (age 36.7+/-1.3 y; body mass index 30.8+/-0.4 kg/m(2)). MEASUREMENTS: Body weight and composition by dual-energy X-ray absorptiometry, blood pressure, serum lipids, lipoproteins, hemostatic factors, glucose, insulin, and leptin at baseline and every 3 months. RESULTS: The FS group lost 6.27 kg of body weight by 9 months vs 4.0 kg in the control and 1.79 kg in the FR groups. There was a significant diet main effect on cholesterol (P=0.002), low-density lipoprotein cholesterol (P=0.003), and triglycerides (P=0.01), all of which decreased in the FS group but not the other groups by 9 months. Apolipoprotein B (ApoB) increased in the FR and control groups but was unchanged in the FS group (diet main effect P=0.04). High-density lipoprotein (HDL) cholesterol increased in all groups over 9 months (time main effect P=0.0001). Time main effects were also observed for cholesterol, ApoA1, ApoB, Factor VII, diastolic blood pressure, and glucose. After adjustment for % fat loss at 9 months, the effects of diet on change in risk factors remained significant only for triglycerides. DISCUSSION: Consumption of a low-fat diet containing olestra for 9 months produced significant improvement in cardiovascular risk factors, an effect largely explained by weight loss. Long-term low-fat diet consumption with or without olestra does not decrease HDL cholesterol.     

A randomized controlled trial of Sweet Talk, a text-messaging system to support young people with diabetes.

AIMS: To assess Sweet Talk, a text-messaging support system designed to enhance self-efficacy, facilitate uptake of intensive insulin therapy and improve glycaemic control in paediatric patients with Type 1 diabetes. METHODS: One hundred and twenty-six patients fulfilled the eligibility criteria; Type 1 diabetes for > 1 year, on conventional insulin therapy, aged 8-18 years. Ninety-two patients were randomized to conventional insulin therapy (n = 28), conventional therapy and Sweet Talk (n = 33) or intensive insulin therapy and Sweet Talk (n = 31). Goal-setting at clinic visits was reinforced by daily text-messages from the Sweet Talk software system, containing personalized goal-specific prompts and messages tailored to patients' age, sex and insulin regimen. RESULTS: HbA(1c) did not change in patients on conventional therapy without or with Sweet Talk (10.3 +/- 1.7 vs. 10.1 +/- 1.7%), but improved in patients randomized to intensive therapy and Sweet Talk (9.2 +/- 2.2%, 95% CI -1.9, -0.5, P < 0.001). Sweet Talk was associated with improvement in diabetes self-efficacy (conventional therapy 56.0 +/- 13.7, conventional therapy plus Sweet Talk 62.1 +/- 6.6, 95% CI +2.6, +7.5, P = 0.003) and self-reported adherence (conventional therapy 70.4 +/- 20.0, conventional therapy plus Sweet Talk 77.2 +/- 16.1, 95% CI +0.4, +17.4, P = 0.042). When surveyed, 82% of patients felt that Sweet Talk had improved their diabetes self-management and 90% wanted to continue receiving messages. CONCLUSIONS: Sweet Talk was associated with improved self-efficacy and adherence; engaging a classically difficult to reach group of young people. While Sweet Talk alone did not improve glycaemic control, it may have had a role in supporting the introduction of intensive insulin therapy. Scheduled, tailored text messaging offers an innovative means of supporting adolescents with diabetes and could be adapted for other health-care settings and chronic diseases.     

High-monounsaturated fat, olive oil-rich diet has effects similar to a high-carbohydrate diet on fasting and postprandial state and metabolic profiles of patients with type 2 diabetes

Whether metabolic control in type 2 diabetes mellitus (DM) is best achieved with the traditional high-carbohydrate (CHO), low-fat diet or a low-CHO, high-fat diet is still controversial. In a randomized crossover study, we compared the effects of a low-fat (30% of daily energy) diet and a high-fat (40% of daily energy), high-monounsaturated-fat diet for 6 weeks each on fasting and postprandial glucose, insulin, and lipoprotein concentrations in 12 patients with well-controlled type 2 DM (fasting blood glucose, 176 +/- 54 mg/dL; hemoglobin A1c, 6.4% +/- 0.7%) and no overt dyslipidemia (serum total cholesterol, 235 +/- 43 mg/dL; triglycerides, 180 +/- 63 mg/dL). Home-prepared foods were used and olive oil was the main edible fat, accounting for 8% and 25% of daily energy requirements in the low-fat and high-fat diets, respectively. For postprandial studies, the same mixed meal containing 36% fat was used in both dietary periods. Body weight and fasting and 6-hour postprandial blood glucose, insulin, and lipoprotein levels were similar after the two diets. The mean incremental area under the curve of serum triglycerides 0 to 6 hours after the challenge meal, adjusted for baseline levels, did not change significantly after the high-fat diet compared with the low-fat diet (1,484 +/- 546 v 1,714 +/- 709 mg x 6 h/dL, respectively, P = .099). Mean postprandial triglyceride levels at 6 hours were increased about 2 times over fasting levels and were still greater than 300 mg/dL after either diet. A diet high in total and monounsaturated fat at the expense of olive oil is a good alternative diet to the traditional low-fat diet for patients with type 2 DM. However, ongoing postprandial hypertriglyceridemia with either diet points to the need for other therapies to decrease triglyceride-rich lipoproteins (TRL) and the inherent atherogenic risk in type 2 diabetics.     

Short-term effects of severe dietary carbohydrate-restriction advice in Type 2 diabetes--a randomized controlled trial.

OBJECTIVE: This study sought to examine the effects of a 3-month programme of dietary advice to restrict carbohydrate intake compared with reduced-portion, low-fat advice in obese subjects with poorly controlled Type 2 diabetes. RESEARCH DESIGN AND METHODS: One hundred and two patients with Type 2 diabetes were recruited across three centres and randomly allocated to receive group education and individual dietary advice. Weight, glycaemic control, lipids and blood pressure were assessed at baseline and 3 months. Dietary quality was assessed at the end of study. RESULTS: Weight loss was greater in the low-carbohydrate (LC) group (-3.55 +/- 0.63, mean +/- sem) vs. -0.92 +/- 0.40 kg, P = 0.001) and cholesterol : high-density lipoprotein (HDL) ratio improved (-0.48 +/- 0.11 vs. -0.10 +/- 0.10, P = 0.01). However, relative saturated fat intake was greater (13.9 +/- 0.71 vs. 11.0 +/- 0.47% of dietary intake, P < 0.001), although absolute intakes were moderate. CONCLUSIONS: Carbohydrate restriction was an effective method of achieving short-term weight loss compared with standard advice, but this was at the expense of an increase in relative saturated fat intake.     

Effects of diet on the cellular insulin binding and the insulin sensitivity in young healthy subjects

Summary To ascertain whether the effects of diet on glucose tolerance and insulin sensitivity are mediated through changes of insulin receptors we have studied insulin binding to monocytes in 24 young volunteers (4 groups of 6) during 2 week periods of different dietary regimens. In group 1 and 2 the subjects had their usual diet plus 1000 kcal per day from sucrose or fat, respectively. Group 3 had an isocaloric diet with a low-sucrose content, while group 4 ate low-fat high carbohydrate diets. Before change of diet the total group of volunteers showed an inverse correlation between insulin binding and average daily sucrose intake (R = − 0.52, p<0.01). An excessive sucrose consumption (group 1) was associated with a reduction both of insulin binding (p<0.05) and insulin sensitivity (p<0.05). The changes of the two variables were parallel (R = 0.95, p<0.05). An abundant fat intake (group 2) was also accompanied by a decrease of insulin binding (p<0.05). However, insulin sensitivity was unaltered (p>0.1). A rise of insulin binding (p<0.05) followed the isocaloric, low-sucrose diet (group 3) whereas the insulin sensitivity was unchanged (p>0.1). After the isocaloric, low-fat diet (group 4) no significant change of insulin binding occurred (p>0.1) whereas the insulin sensitivity increased (p<0.05). We conclude that diet and especially the dietary sucrose content affect insulin binding to human monocytes. Evidence is presented that changes of insulin sensitivity following hyperalimentation of sucrose may be induced through alterations of insulin receptors.     

Hypoglycaemia with insulin aspart: a double-blind, randomised, crossover trial in subjects with Type 1 diabetes.

AIMS: To compare the effects of the rapid-acting insulin analogue insulin aspart and soluble human insulin on hypoglycaemia and glycaemic control in patients with Type 1 diabetes when injected immediately before meals as part of intensive insulin therapy. METHODS: In this multinational, double-blind, randomised, crossover trial, 155 patients with Type 1 diabetes (HbA(1c) < 8.0%) were symmetrically randomised to two 16-week treatment periods on either type of insulin, both injected 0-5 min before meals. NPH insulin was given as basal insulin once or twice daily as needed, and insulin dosages were regularly adjusted using pre-defined algorithms to maintain tight glycaemic control. Treatment periods were separated by a 4-week washout. RESULTS: The rate of major nocturnal (24.00-06.00 h) hypoglycaemic episodes was 72% lower with insulin aspart than with human insulin (0.067 vs. 0.225 events/month; P = 0.001). Total rate of major hypoglycaemia did not differ significantly between treatments (insulin aspart/human insulin relative risk 0.72; 95% CI 0.47-1.09, P = 0.12). The rate of minor events was significantly reduced by 7% with insulin aspart (P = 0.048). Reductions in rate of hypoglycaemia were achieved with maintained overall glycaemic control: Mean HbA(1c) remained constant, slightly below 7.7% on both treatments. CONCLUSIONS: The use of insulin aspart in an intensive insulin regimen in patients with tightly controlled Type 1 diabetes led to clinically significant reductions in major nocturnal hypoglycaemia with no deterioration in glycaemic control. Major nocturnal hypoglycaemia appears to be a strong clinical indication for the use of rapid-acting insulin analogues during intensive insulin therapy.     

Sustained effects of pioglitazone vs. glibenclamide on insulin sensitivity, glycaemic control, and lipid profiles in patients with Type 2 diabetes.

AIMS: This study compared the effects of 52 weeks' treatment with pioglitazone, a thiazolidinedione that reduces insulin resistance, and glibenclamide, on insulin sensitivity, glycaemic control, and lipids in patients with Type 2 diabetes. METHODS: Patients with Type 2 diabetes were randomized to receive either pioglitazone (initially 30 mg QD, n = 91) or micronized glibenclamide (initially 1.75 mg QD, n = 109) as monotherapy. Doses were titrated (to 45 mg for pioglitazone and 10.5 mg for glibenclamide) to achieve glycaemic targets during the next 12 weeks: fasting blood glucose of < or = 7 mmol/l and 1-h postprandial blood glucose of < or = 10 mmol/l. Patients were maintained on the titrated dose for 40 weeks. RESULTS: Pioglitazone significantly increased insulin sensitivity compared with glibenclamide, as assessed by homeostasis model assessment (17.0% vs. -13.0%; P < 0.001), quantitative insulin sensitivity check index (0.011 vs. -0.007; P < 0.001) and fasting serum insulin (-1.3 pmol/l vs. 23.8 pmol/l; P = 0.007). The glibenclamide group had significantly lower HbA1c than the pioglitazone group after 12 weeks of therapy (7.8% vs. 8.3%, P = 0.015), but significantly higher HbA1c after 52 weeks of therapy (7.8% vs. 7.2%, P = 0.001). Pioglitazone significantly (vs. glibenclamide) increased mean HDL-C (P < 0.001), decreased mean triglycerides (P = 0.019), and decreased mean atherogenic index of plasma (AIP; P = 0.001) and mean total cholesterol/HDL-C (P = 0.004), without significantly elevating mean total cholesterol or mean LDL-C compared with glibenclamide. CONCLUSIONS These data suggest that the effects of pioglitazone are more sustained than those of glibenclamide for improving insulin sensitivity in patients with Type 2 diabetes, and that 52 weeks' treatment with pioglitazone has favourable effects on glycaemic control and lipoprotein profile.     

Moderate protein intake improves total and regional body composition and insulin sensitivity in overweight adults

A high protein intake (approximately 40% of energy intake) combined with aerobic and resistance exercise training is more closely associated with improved body composition and cardiovascular risk profile than a traditional protein intake (approximately 15% of intake) combined with moderate-intensity aerobic exercise. However, there is concern that such high-protein diets may adversely affect health. We therefore tested the hypothesis that moderate protein intake (approximately 25% of energy intake) would elicit similar benefits on body composition and metabolic profile as high protein intake. Twenty-four overweight/obese men and women (body mass index [BMI] = 32.2 +/- 3.4, percentage of body fat [%BF] = 37.3 +/- 8.0) were matched for BMI and %BF and randomly assigned to one of 3 groups for a 3-month nutrition/exercise training intervention: (1) high-protein diet (approximately 40% of energy intake) and combined high-intensity resistance and cardiovascular training (HPEx, n = 8, 5 female and 3 male), (2) moderate-protein diet (approximately 25% of energy intake) and combined high-intensity resistance and cardiovascular training (MPEx, n = 8, 5 female and 3 male), or (3) high-protein diet only (HPNx, n = 8, 5 female and 3 male). Total and regional body composition (dual-energy x-ray absorptiometry), insulin sensitivity (insulin sensitivity index to the oral glucose tolerance test), insulin-like growth factor-1 (IGF-1), IGF binding protein-1 (IGFBP-1), IGF binding protein-3 (IGFBP-3), and blood lipids were measured at baseline and after the intervention. All groups experienced significant (P < .05) and similar losses of body weight, BMI, and total and abdominal %BF, and similar improvements in insulin sensitivity (HPEx, 6.3 +/- 1.2 vs 9.5 +/- 0.98; MPEx, 6.2 +/- 1.4 vs 8.4 +/- 1.6; HPNx, 3.7 +/- 1.1 vs 7.0 +/- 1.1; insulin sensitivity index to the oral glucose tolerance test; P < .05) and leptin levels. Furthermore, the HPEx group demonstrated decreases in total cholesterol (TC) and triglycerides, and increases in IGF-1 and IGFBP-1. The MPEx group experienced decreases in TC, whereas the HPNx group had increases in high-density lipoprotein cholesterol, TC to high-density lipoprotein, IGF-1, and IGFBP-1. In conclusion, moderate protein intake elicits similar benefits in body composition and insulin sensitivity as a high-protein diet. These findings may have practical implications for individuals interested in diets containing elevated dietary protein.     

Beta-cell function evaluated by HOMA as a predictor of secondary sulphonylurea failure in Type 2 diabetes.

BACKGROUND AND AIMS: Secondary failure to oral hypoglycaemic agents, a common evolution of long-standing Type 2 diabetes, is usually assessed by non-standardized indices requiring fine clinical assessment, including hyperglycaemia resistant to maximum doses of sulphonylureas despite appropriate diet and follow-up. The goal of this study was to evaluate if HOMA, a modelized plasma insulin/glucose ratio allowing simple evaluation of residual insulin secretion and sensitivity, is a better predictor of the insulin requiring stage than clinical indices. MATERIALS AND METHODS: HOMA was measured in 84 Type 2 diabetic patients aged 58 +/- SD 6 years, with diabetes duration 11 +/- 4 years, hospitalized because of hyperglycaemia resistant to maximal doses of sulphonylureas (e.g. glibenclamide > or = 15 mg/day), with no apparent external reason for hyperglycaemia. Despite reinforced appropriate diet recommendations, 62 of these patients remained hyperglycaemic (insulin-requiring group). RESULTS: Age, duration of diabetes, body mass index (BMI) and HOMA value for insulin sensitivity (71 +/- 6% vs. 76 +/- 7%, normal values 59-161%) were comparable in the two groups. HbA(1c) was higher (10.0 +/- 0.2% vs. 8.3 +/- 0.3%, P < 0.001) and HOMA insulin secretion values lower (25 +/- 2% vs. 43 +/- 6%, normal values 70-150%, P < 0.01) in the insulin-requiring group. Of the following potential predictors: HbA(1c) > 8%, duration of diabetes > or = 10 years, HbA(1c) combined with diabetes duration, insulin sensitivity < or = 40%, insulin secretion < or = 20%, the latter showed the best positive predictivity (86% patients with low insulin secretion were insulin-requiring). CONCLUSIONS: (i) HOMA is a simple and good predictor of the insulin-requiring stage in Type 2 diabetes mellitus; (ii) this stage of diabetes is characterized by a further decline of insulin secretion rather than of insulin sensitivity. Diabet. Med. 18, 584-588 (2001)     

Beneficial effect of a low glycaemic index diet in type 2 diabetes.

Low glycaemic index foods produce low blood glucose and insulin responses in normal subjects, and improve blood glucose control in Type 1 and well-controlled Type 2 diabetic patients. We studied the effects of a low glycaemic index diet in 15 Type 2 diabetic patients with a mean fasting blood glucose of 9.5 mmol l-1 using a randomized, crossover design. Patients were given pre-weighed diets (59% energy as carbohydrate, 21% fat, and 24 g 1000-kcal-1 dietary fibre) for two 2-week periods, with a diet glycaemic index of 60 during one period and 87 during the other. On the low glycaemic index diet, the blood glucose response after a representative breakfast was 29% less than on the high glycaemic index diet (874 +/- 108 (+/- SE) vs 204 +/- 112 mmol min l-1; p less than 0.001), the percentage reduction being almost identical to the 28% difference predicted from the meal glycaemic index values. After the 2-week low glycaemic index diet, fasting serum fructosamine and cholesterol levels were significantly less than after the high glycaemic index diet (3.17 +/- 0.12 vs 3.28 +/- 0.16 mmol l-1, p less than 0.05, and 5.5 +/- 0.4 vs 5.9 +/- 0.5 mmol l-1, p less than 0.02, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of improved post-prandial blood glucose control on post-prandial metabolism and markers of vascular risk in people with Type 2 diabetes

A variety of abnormalities of metabolic, haemostatic and endothelial markers are associated with Type 2 diabetes. Evidence suggests that poor post-prandial blood glucose control may contribute to vascular risk. We aimed to examine whether the restoration of a more physiological insulin profile post-prandially would improve these abnormalities. Twenty-one patients with insulin-treated Type 2 diabetes were recruited into a single centre, crossover, double-blind study. Patients were randomized to unmodified human insulin or insulin aspart before main meals for 6-week study periods, both together with NPH insulin. At the end of each study period, pre-breakfast levels of markers of vascular risk were assessed and a test meal performed. There was no significant difference in HbA(1c) (7.04 +/- 0.13% (+/-S.E.) versus 7.15 +/- 0.11%, P = 0.060) with insulin aspart compared to human insulin at the end of each study period. The mean post-prandial blood glucose concentration at 90 min from self-monitored results was lower with insulin aspart than with human insulin (7.9 +/- 0.4 mmol/l versus 9.3 +/- 0.4 mmol/l, P = 0.011) as was study day post-prandial blood glucose at 90 min (8.4 +/- 0.5 mmol/l versus 9.2 +/- 0.6 mmol/l, P = 0.046). No significant differences were found in fasting lipid profile, apolipoproteins, fibrinogen, plasminogen activator inhibitor-1, E-selectin, or homocysteine between the two study periods. Insulin aspart resulted in improved post-prandial glycaemic control when compared to human insulin in Type 2 diabetic patients, but this was not associated with changes in markers of vascular risk.     

Treatment with insulin glargine does not suppress serum IGF-1.

AIMS: A 6-8-fold higher insulin-like growth factor 1 (IGF-1) receptor binding affinity in vitro is reported for the insulin analogue glargine compared with human insulin. This study evaluates the in vivo significance by exploring the growth hormone (GH)-IGF-1 axis. Assuming a higher binding affinity of insulin glargine to pituitary IGF-1 receptors, serum IGF-1 concentrations should decrease via negative feedback. METHODS: In a crossover study, insulin glargine or NPH insulin, respectively, were used in identical doses as basal insulins in treatment periods of 3 weeks. RESULTS: Overall glycaemic control was not different between the treatment regimens. In contrast to the hypothesis, serum IGF-1 concentrations were higher during insulin glargine treatment compared with NPH insulin in patients with Type 1 diabetes (177 +/- 18 vs. 159 +/- 18 microg/l, P < 0.02, n = 17, age 28 +/- 2 years). The effect on IGF-1 was most pronounced in male patients with Type 1 diabetes (174 +/- 11 vs. 146 +/- 10 microg/l, P < 0.02, n = 10), but was not significant in patients with Type 2 diabetes (92 +/- 9 vs. 86 +/- 8 microg/l, NS, n = 25, age 66 +/- 2 years). CONCLUSIONS: In contrast to our hypothesis, serum IGF-1 did not decrease, but rose during insulin glargine treatment, suggesting an absence of relevant IGF-1-like activity of glargine at the level of the pituitary. Improved plasma glucose at dawn during glargine treatment may intensify growth hormone surges and increase IGF-1 synthesis. Significant increases were seen in younger patients, compatible with the higher activity of the GH-IGF-1 axis in this age group.     

Physical activity and energy intake in adolescent girls with Type 1 diabetes.

AIMS: Girls with Type 1 diabetes often gain excessive weight during puberty. The aims of this study were to compare objectively assessed physical activity and energy intake in girls with Type 1 diabetes with those in healthy age-matched controls. METHODS: This prospective cohort study comprised 26 girls with Type 1 diabetes and 49 control girls. The mean age of the diabetic girls was 15.7 +/- 2.1 years and that of the control girls 15.8 +/- 2.1 years. In the diabetic group, mean haemoglobin A1c was 7.6 +/- 1.4% and daily insulin dosage was 1.1 +/- 0.3 U/kg. Physical activity was measured during 7 consecutive days with a uniaxial accelerometer, and energy intake was assessed concurrently with a 7-day food diary. RESULTS: There was a tendency towards lower total amount of physical activity in the diabetes group but the difference between the study groups did not reach statistical significance (Diabetes: 464 +/- 123 counts/min/day; Controls: 523 +/- 138 counts/min/day; P = 0.06). No difference was found between the groups regarding total energy intake (Diabetes: 8.5 +/- 1.8 MJ/day; Controls: 8.4 +/- 2.6 MJ/day). The carbohydrate intake was lower and the protein and fibre intakes were higher in girls with diabetes. No association was observed between physical activity, energy intake and HbA1c. CONCLUSIONS: In this prospective cohort study, we found a tendency towards lower physical activity but no differences in energy intake between girls with Type 1 diabetes and age-matched controls. Larger studies are needed to further explore the importance of the total amount of physical activity for excessive weight gain in adolescent girls with Type 1 diabetes.     

Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes

OBJECTIVE: Low levels of testosterone in men have been shown to be associated with type 2 diabetes, visceral adiposity, dyslipidaemia and metabolic syndrome. We investigated the effect of testosterone treatment on insulin resistance and glycaemic control in hypogonadal men with type 2 diabetes. DESIGN: This was a double-blind placebo-controlled crossover study in 24 hypogonadal men (10 treated with insulin) over the age of 30 years with type 2 diabetes. METHODS: Patients were treated with i.m. testosterone 200 mg every 2 weeks or placebo for 3 months in random order, followed by a washout period of 1 month before the alternate treatment phase. The primary outcomes were changes in fasting insulin sensitivity (as measured by homeostatic model index (HOMA) in those not on insulin), fasting blood glucose and glycated haemoglobin. The secondary outcomes were changes in body composition, fasting lipids and blood pressure. Statistical analysis was performed on the delta values, with the treatment effect of placebo compared against the treatment effect of testosterone. RESULTS: Testosterone therapy reduced the HOMA index (-1.73 +/- 0.67, P = 0.02, n = 14), indicating an improved fasting insulin sensitivity. Glycated haemoglobin was also reduced (-0.37 +/- 0.17%, P = 0.03), as was the fasting blood glucose (-1.58 +/- 0.68 mmol/l, P = 0.03). Testosterone treatment resulted in a reduction in visceral adiposity as assessed by waist circumference (-1.63 +/- 0.71 cm, P = 0.03) and waist/hip ratio (-0.03 +/- 0.01, P = 0.01). Total cholesterol decreased with testosterone therapy (-0.4 +/- 0.17 mmol/l, P = 0.03) but no effect on blood pressure was observed. CONCLUSIONS: Testosterone replacement therapy reduces insulin resistance and improves glycaemic control in hypogonadal men with type 2 diabetes. Improvements in glycaemic control, insulin resistance, cholesterol and visceral adiposity together represent an overall reduction in cardiovascular risk.