Association of prenatal exposure to gestational diabetes with offspring body composition and regional body fat distribution.

The aim of this cohort study was to compare body composition and regional body fat distribution between children exposed (GDM+) or unexposed (GDM-) in utero to gestational diabetes mellitus (GDM) and to investigate the association with the glycaemic and the insulin profile. Data from 56 GDM+ and 30 GDM- were analysed. Height, weight and waist circumference were measured. Total and regional body composition was measured by dual-energy X-ray absorptiometry. Insulin, glucose and HbA1c were obtained from a fasting plasma sample, and the HOMA-IR index was calculated. anova was performed to compare adiposity measures between GDM+ and GDM-. Associations between the glycaemic and insulin profile and adiposity measures were studied using partial Pearson correlations. Mean age was 6.6 ± 2.3 years. Waist circumference, fat mass percentage, android fat mass, android fat mass percentage and android-to-gynoid fat mass ratio were higher among GDM+, and lean mass percentage was lower (P < 0.05). Among GDM+ children, body mass index (BMI) z score, waist circumference, fat mass percentage, android fat mass percentage and android-to-gynoid fat mass ratio were all positively correlated with HbA1C (r = 0.32-0.43, P < 0.05). Prenatal exposure to GDM is associated with increased total and abdominal adiposity. This increased adiposity observed among GDM+ children is associated with an altered glycaemic profile. This study is registered in the Clinical Trials.gov registry (NCT01340924).

Strawberry and cranberry polyphenols improve insulin sensitivity in insulin-resistant, non-diabetic adults: a parallel, double-blind, controlled and randomised clinical trial.

Plant-derived foods rich in polyphenols are associated with several cardiometabolic health benefits, such as reduced postprandial hyperglycaemia. However, their impact on whole-body insulin sensitivity using the hyperinsulinaemic-euglycaemic clamp technique remains under-studied. We aimed to determine the effects of strawberry and cranberry polyphenols (SCP) on insulin sensitivity, glucose tolerance, insulin secretion, lipid profile, inflammation and oxidative stress markers in free-living insulin-resistant overweight or obese human subjects (n 41) in a parallel, double-blind, controlled and randomised clinical trial. The experimental group consumed an SCP beverage (333 mg SCP) daily for 6 weeks, whereas the Control group received a flavour-matched Control beverage that contained 0 mg SCP. At the beginning and at the end of the experimental period, insulin sensitivity was assessed by a hyperinsulinaemic-euglycaemic clamp, and glucose tolerance and insulin secretion by a 2-h oral glucose tolerance test (OGTT). Insulin sensitivity increased in the SCP group as compared with the Control group (+0·9 (sem 0·5)×10-3 v. -0·5 (sem 0·5)×10-3 mg/kg per min per pmol, respectively, P=0·03). Compared with the Control group, the SCP group had a lower first-phase insulin secretion response as measured by C-peptide levels during the first 30 min of the OGTT (P=0·002). No differences were detected between the two groups for lipids and markers of inflammation and oxidative stress. A 6-week dietary intervention with 333 mg of polyphenols from strawberries and cranberries improved insulin sensitivity in overweight and obese non-diabetic, insulin-resistant human subjects but was not effective in improving other cardiometabolic risk factors.

An explained variance-based genetic risk score associated with gestational diabetes antecedent and with progression to pre-diabetes and type 2 diabetes: a cohort study.

OBJECTIVE: To determine whether an explained-variance genetic risk score (GRS), with 36 single nucleotide polymorphisms (SNPs) previously associated with type 2 diabetes (T2D), is also associated with gestational diabetes mellitus (GDM), and with the progression to pre-diabetes and T2D among women with prior GDM. DESIGN: A cohort study. SETTING: Clinical investigation unit of Laval University, Quebec, Canada. POPULATION: A cohort of 214 women with prior GDM and 82 controls recruited between 2009 and 2012. METHODS: Associations between the GRS and GDM. MAIN OUTCOMES MEASURES: GDM and prevalence of pre-diabetes and T2D. RESULTS: Women with prior GDM had a higher GRS compared with controls (38.6 ± 3.9, 95% CI 38.1-39.1, versus 37.4 ± 3.2, 95% CI 36.7-38.1; P < 0.0001). In women with prior GDM, the explained-variance GRS was higher for pre-diabetic women compared with women who remained normoglucotolerant at testing (1.21 ± 0.18, 95% CI 1.18-1.23, versus 1.17 ± 0.15, 95% CI 1.13-1.20; P < 0.0001). Similarly, women with T2D had a higher explained-variance GRS compared with women with prior GDM who remained normoglucotolerant (1.20 ± 0.18, 95% CI 1.14-1.25, versus 1.17 ± 0.17, 95% CI 1.13-1.20; P < 0.0001). The predictive effects of the explained-variance GRS, age, and body mass index (BMI), or the additive effects of the three variables, were tested for pre-diabetes and T2D. We observed an area under the curve of 0.6269 (95% CI 0.5638-0.6901) for age and BMI, and adding the explained-variance GRS into the model increased the area to 0.6672 (95% CI 0.6064-0.7281) for the prediction of pre-diabetes. CONCLUSIONS: An explained-variance GRS is associated with both GDM and progression to pre-diabetes and T2D in women with prior GDM.

The Barriers to Physical Activity in Type 1 Diabetes (BAPAD-1) scale: predictive validity and reliability.

AIM: Perceived barriers are one determinant of physical activity. Depending on the study population, these barriers can vary. The aim of this study was to assess the reliability and predictive validity of the 'Barriers to Physical Activity in Type 1 Diabetes' (BAPAD-1) scale, developed by Dubé et al. METHODS: A total of 77 adults (48% women; age: 43.5±10.4; body mass index: 25.2±4.3kg/m(2); HbA(1c): 7.6±1.3%) with type 1 diabetes completed the questionnaire and an evaluation of their physical activity using an accelerometer (8.4±1.2 days) and cardiorespiratory fitness assessment (VO(2)(peak)). To evaluate the temporal stability of the questionnaire, a subgroup of 17 participants answered the BAPAD-1 scale on both visits required by the protocol (10±4 days). RESULTS: The BAPAD-1 scale showed good internal validity with an inter-items correlation coefficient (Cronbach's correlation) of 0.85. The intraclass correlation coefficient for the two times the scales were completed was 0.80. The BAPAD-1 score was negatively correlated with both physical activity energy expenditure (r=-0.25; P=0.03) and VO(2)(peak) adjusted for gender and age (r=-0.27; P=0.02). CONCLUSION: The BAPAD-1 scale is a reliable and valid tool for assessing salient barriers to physical activity. In future, this scale could be used to describe the factors accounting for physical activity, and for planning interventions aimed at promoting physical activity among adults with type 1 diabetes.

Effect of sitagliptin therapy on postprandial lipoprotein levels in patients with type 2 diabetes.

AIM: Recent studies indicate that type 2 diabetes is associated with an increased secretion of both hepatic and intestinal lipoproteins, leading to the accumulation of atherogenic triglyceride (TG)-rich lipoproteins. Sitagliptin is a selective inhibitor of dipeptidyl peptidase-4 that has been shown to reduce fasting and postprandial glucose levels in patients with type 2 diabetes presumably through incretin hormone-mediated improvements in islet function. The objective of the present study is to examine the effects of treatment with sitagliptin on postprandial lipid and incretin hormone levels as well as glucose homeostasis in patients with type 2 diabetes. METHODS: Thirty-six subjects with type 2 diabetes (30 men/6 postmenopausal women with a mean age of 58.1 ± 6.4 years and a body mass index of 30.7 ± 4.9 kg/m(2) ) were recruited in this double-blind cross-over study using sitagliptin 100 mg/day or placebo for a 6-week period each, with a 4-week washout period between the two phases. At the end of each phase of treatment, patients underwent an oral lipid tolerance test providing 35 g of fat per m(2) of body surface area and blood samples were taken over an 8-h period. RESULTS: Sitagliptin therapy significantly decreased the postprandial area under the curves (AUCs) for plasma apolipoprotein (apo)B (-5.1%, p = 0.002), apoB-48 (-7.8%, p = 0.03), TG (-9.4%, p = 0.006), very low-density lipoprotein (VLDL)-cholesterol (-9.3%, p = 0.001), free fatty acids (FFAs) (-7.6%, p = 0.005) and glucose (-9.7%, p < 0.0001). Furthermore, the postprandial AUCs for plasma intact glucagon-like peptide-1 (+67.8%, p < 0.0001) and glucose-dependent insulinotropic polypeptide (+67.3%, p < 0.0001) were significantly increased following treatment with sitagliptin, whereas the AUC for plasma glucagon was reduced by -9.7% (p = 0.001) with no significant changes in the AUCs for plasma insulin and C-peptide. Sitagliptin therapy also improved homeostasis model assessment (HOMA) index for insulin resistance (-14.6%, p = 0.01) and ß-cell function (+32.3%, p = 0.007). CONCLUSIONS: Treatment with sitagliptin for 6 weeks reduced postprandial plasma levels of TG-rich lipoproteins of both intestinal and hepatic origin, most likely by increasing incretin hormone levels, reducing circulating plasma FFA concentrations and improving insulin sensitivity and ß-cell function.

Relationship of mid-thigh adiposity to the metabolic syndrome in postmenopausal women.

BACKGROUND: In postmenopausal women, a population at risk for the metabolic syndrome, the relative contribution of central fat versus peripheral muscle fat to the metabolic risk profile is unknown. This study explored the relationship between muscle fat infiltration derived from computed tomography (CT) scans and metabolic syndrome. METHODS: Mid-thigh CT scans measured the surface of muscle with low attenuation (LAMS) [0-34 Hounsfield units (HU)], which represented the specific component of fat-rich muscle. Insulin sensitivity was evaluated by an euglycemic-hyperinsulinemic clamp. National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria were used to determine the presence of the metabolic syndrome. RESULTS: A total of 103 postmenopausal women were studied. Metabolic syndrome was found in 43 women with significantly higher levels of abdominal adiposity, higher LAMS (27 +/- 8 vs. 23 +/- 7 cm(2)), and lower insulin sensitivity compared to those without the metabolic syndrome. Women with higher levels of LAMS presented higher metabolic risk features such as higher blood pressure, abdominal adiposity, inflammatory markers, and blood lipid levels. LAMS and visceral adipose tissue correlated significantly with the presence of metabolic syndrome, but these relationships were lost when LAMS was adjusted for visceral adipose tissue but not when visceral adipose tissue was adjusted for LAMS. CONCLUSIONS: These results suggest that postmenopausal women who present with metabolic syndrome had increased fat-rich mid-thigh muscle. Moreover, women with more fat-rich muscle had many features of the metabolic syndrome. These relations were weakened when visceral adipose tissue was taken into account suggesting that LAMS may play a relatively smaller role, compared to VAT, in the contribution to the metabolic syndrome.

Improvements in glucose homeostasis in response to regular exercise are influenced by the PPARG Pro12Ala variant: results from the HERITAGE Family Study.

AIMS/HYPOTHESIS: Exercise training improves glucose homeostasis, but large inter-individual differences are reported, suggesting a role of genetic factors. We investigated whether variants either confirmed or newly identified as diabetes susceptibility variants through genome-wide association studies (GWAS) modulate changes in phenotypes derived from an IVGTT in response to an endurance training programme. METHODS: We analysed eight polymorphisms in seven type 2 diabetes genes (CDKAL1 rs7756992; CDKN2A and CDKN2B rs10811661 and rs564398; HHEX rs7923837; IGF2BP2 rs4402960; KCNJ11 rs5215; PPARG rs1801282; and TCF7L2 rs7903146) in a maximum of 481 sedentary, non-diabetic white individuals, who participated in a 20-week endurance training programme. Associations were tested between the variants and changes in IVGTT-derived phenotypes. RESULTS: The only evidence of association with training response was found with PPARG rs1801282 (Pro12Ala). We observed that Ala carriers experienced greater increase in overall glucose tolerance (Deltaglucose disappearance index Ala/Ala 0.22 +/- 0.22, Pro/Ala 0.14 +/- 0.06, Pro/Pro 0.004 +/- 0.03; p = 0.0008), glucose effectiveness (Ala/Ala 0.28 +/- 0.41, Pro/Ala 0.44 +/- 0.14, Pro/Pro 0.09 +/- 0.06; p = 0.004), acute insulin response to glucose (Ala/Ala 64.21 +/- 37.73, Pro/Ala -11.92 +/- 40.30, Pro/Pro -46.30 +/- 14.70; p = 0.03) and disposition index (Ala/Ala 551.8 +/- 448.5, Pro/Ala 534.6 +/- 218.3, Pro/Pro -7.44 +/- 88.18; p = 0.003). CONCLUSIONS/INTERPRETATION: Compared with Pro/Pro individuals, PPARG Ala carriers experienced greater improvements in glucose and insulin metabolism in response to regular endurance training. However, we did not find evidence of association between type 2 diabetes susceptibility variants recently identified through GWAS and glucose homeostasis response to exercise. Our results extend those of previous studies showing that Ala carriers appear to be more responsive to beneficial health effects of lifestyle interventions.

Using restrictive messages to limit high-fat foods or nonrestrictive messages to increase fruit and vegetable intake: what works better for postmenopausal women?

BACKGROUND/OBJECTIVES: To compare the effects of two dietary approaches on changes in dietary intakes and body weight: (1) an approach emphasizing nonrestrictive messages directed toward the inclusion of fruits and vegetables (HIFV) and (2) another approach using restrictive messages to limit high-fat foods (LOFAT). SUBJECTS/METHODS: A total of 68 overweight-obese postmenopausal women were randomly assigned to one of the two dietary approaches. The 6-month dietary intervention included three group sessions and ten individual sessions with a dietitian. Dietary food intake and anthropometric variables were measured at baseline, at 3 months and at 6 months. RESULTS: Energy density decreased in both groups after the intervention compared with baseline (HIFV, -0.3+/-0.2 kcal/g; LOFAT, -0.3+/-0.3 kcal/g; P<0.0001). Although body weight decreased significantly in both groups after the intervention compared with baseline (HIFV, -1.6+/-2.9 kg; LOFAT, -3.5+/-2.9 kg; P<0.0001), women in the LOFAT group lost significantly more body weight than women in the HIFV group (P=0.01). In the HIFV group, the decrease in energy density was found to be an independent predictor of body weight loss. CONCLUSIONS: The LOFAT approach induces more weight loss than does the HIFV approach in our sample of overweight-obese postmenopausal women.

Validation of a simple index (SIisOGTT) of insulin sensitivity in a population of sedentary men.

AIM: The ongoing obesity epidemic is associated with numerous health problems related to altered metabolic function. Among these is type 2 diabetes, characterized by lowered insulin sensitivity (IS). Consequently, the development of simple indices to assess IS has research and clinical importance. The SI(is)OGTT, a new index of IS, was recently described by Bastard et al. (Diabetes & Metabolism 2007;33:261-8), and validated in sedentary, non-diabetic, overweight and obese postmenopausal women. The aim of the present study was to validate the index in men. METHODS: The data used in this project came from sedentary men (n=36), aged 34-53 years, all of whom underwent a hyperinsulinaemic-euglycaemic clamp and 2-hour oral glucose tolerance test (OGTT). Correlations with M/I (glucose infusion rate [GIR] divided by insulin concentration), GIR and GIR divided by fat-free mass (FFM) were obtained by four well-known indices (HOMA, QUICKI, Cederholm and Matsuda) as well as with the new SI(is)OGTT index. Pearson correlations and Bland-Altman analyses were obtained for every index versus clamp value. RESULTS: The best correlate of IS in the present study was the SI(is)OGTT (r=0.84, P<0.0001). The agreement of this method with the hyperinsulinaemic-euglycaemic clamp, as assessed by Bland-Altman plots, was similar to those of the other indices and to those previously described in postmenopausal women. CONCLUSION: The new index proposed by Bastard et al. is as good a predictor of IS in sedentary men as the other commonly used indices, and appears to be as reliable in this population as it was in the original study of postmenopausal women.

Evidence for interaction between PPARG Pro12Ala and PPARGC1A Gly482Ser polymorphisms in determining type 2 diabetes intermediate phenotypes in overweight subjects.

BACKGROUND: The peroxisome proliferator-activated receptor-gamma ( PPARG) Pro12Ala and the PPARG co-activator-1alpha ( PPARGC1A) Gly482Ser polymorphisms (SNPs) have been associated with type 2 diabetes mellitus (T2DM) risk. We hypothesized that independent and interactive effects of the PPARG Pro12Ala and PPARGC1A Gly482Ser polymorphisms influence T2DM intermediate phenotypes. MATERIAL AND METHODS: PPARG Pro12Ala and PPARGC1A Gly482Ser SNPs were studied in 680 non diabetic subjects who underwent a 75 g oral glucose tolerant test (OGTT). Glucose and insulin plasma levels in the fasting state and derived from the OGTT were included in the present study. RESULTS: We found significant independent effects of the PPARG and PPARGC1A variants on fasting insulin levels (p=0.02 for both), HOMA-IR (p=0.03 and p=0.02, respectively), insulin area under the curve (AUC) (p=0.007 and p=0.006, respectively) and 2-h glucose levels (p=0.02 for PPARGC1A). Furthermore, significant gene-gene interactions were found for fasting insulin, HOMA-IR and insulin AUC (p=0.03 for all). Carriers of the PPARGC1A Gly allele who were also PPARG Ala-carriers had higher fasting insulin levels (p=0.02), HOMA-IR (p=0.01) and insulin AUC (p=0.01) compared to the Ser/Ser-Ala+genotype combination, whereas no differences between the PPARGC1A genotypes among the PPARG Pro/Pro carriers were observed. CONCLUSION: Together, these results showed that PPARG Pro12Ala and PPARGC1A Gly482Ser variants are associated, alone and in interaction, with insulin and glucose homeostasis and suggest that gene-gene interactions should be taken into account in candidate gene studies of T2DM to identify subjects with markedly different risks of developing the disease.

Associations between glucose tolerance, insulin sensitivity and insulin secretion phenotypes and polymorphisms in adiponectin and adiponectin receptor genes in the Quebec Family Study.

AIMS: Studies suggest that adiponectin (APM1) and its receptors 1 and 2 (AdipoR1 and AdipoR2) play an important role in the development of insulin resistance (IR). Our objective was to examine associations between APM1 (+45T>G, +276G>T and -3971A>G), AdipoR1 (-100G>T and -3882T>C) and AdipoR2 (-35361A>G and -1352G>A) genes single-nucleotide polymorphisms (SNPs) and adiponectin plasma levels, indicators of glucose tolerance, insulin sensitivity (IS) and insulin secretion. METHODS: Six hundred and twenty-two non-diabetic subjects from the Quebec Family Study (QFS) underwent a 75-g oral glucose tolerance test (OGTT), with measurement of fasting adiponectin, glucose, insulin and C-peptide levels. Indices of glucose tolerance, IS and insulin secretion were derived from fasting and OGTT measurements. RESULTS: Significant evidence of association was found between indices of IS and APM1 and AdipoR1 SNPs. The APM1 -3971G/G homozygotes exhibited a reduced area under the curve of insulin during the OGTT (P = 0.007) and higher Cederholm index (P = 0.01) compared to the A/A homozygotes. The APM1+45T>G variant was also associated with fasting (P = 0.002) and 2-h (P = 0.007) glucose values as well as with higher Cederholm index (P = 0.04) and disposition index (P = 0.02). Finally, the AdipoR1-3882T>C SNP was associated with fasting glucose (P = 0.03), the homeostasis model assessment for insulin resistance (P = 0.04) and an index of insulin secretion (P30/G30, P = 0.02). No evidence of association was found with plasma adiponectin levels. CONCLUSIONS: These results provide evidence for an influence of common SNPs in the APM1 and AdipoR1 genes on different phenotypes of glucose and insulin metabolism associated with increased risk of type 2 diabetes.

Substrate source utilization during moderate intensity exercise with glucose ingestion in Type 1 diabetic patients.

Substrate oxidation and the respective contributions of exogenous glucose, glucose released from the liver, and muscle glycogen oxidation were measured by indirect respiratory calorimetry combined with tracer technique in eight control subjects and eight diabetic patients (5 men and 3 women in both groups) of similar age, height, body mass, and maximal oxygen uptake, over a 60-min exercise period on cycle ergometer at 50.8% (SD 4.0) maximal oxygen uptake [131.0 W (SD 38.2)]. The subjects and patients ingested a breakfast (containing approximately 80 g of carbohydrates) 3 h before and 30 g of glucose (labeled with 13C) 15 min before the beginning of exercise. The diabetic patients also received their usual insulin dose [Humalog = 9.1 U (SD 0.9); Humulin N = 13.9 U (SD 4.4)] immediately before the breakfast. Over the last 30 min of exercise, the oxidation of carbohydrate [1.32 g/min (SD 0.48) and 1.42 g/min (SD 0.63)] and fat [0.33 g/min (SD 0.10) and 0.30 g/min (SD 0.10)] and their contribution to the energy yield were not significantly different in the control subjects and diabetic patients. Exogenous glucose oxidation was also not significantly different in the control subjects and diabetic patients [6.3 g/30 min (SD 1.3) and 5.2 g/30 min (SD 1.6), respectively]. In contrast, the oxidation of plasma glucose and oxidation of glucose released from the liver were significantly lower in the diabetic patients than in control subjects [14.5 g/30 min (SD 4.3) and 9.3 g/30 min (SD 2.8) vs. 27.9 g/30 min (SD 13.3) and 21.6 g/30 min (SD 12.8), respectively], whereas that of muscle glycogen was significantly higher [28.1 g/30 min (SD 15.5) vs. 11.6 g/30 min (SD 8.1)]. These data indicate that, compared with control subjects, in diabetic patients fed glucose before exercise, substrate oxidation and exogenous glucose oxidation overall are similar but plasma glucose oxidation is lower; this is associated with a compensatory higher utilization of muscle glycogen.

Disinhibition, as assessed by the Three-Factor Eating Questionnaire, is inversely related to psychological well-being in postmenopausal women.

UNLABELLED: Psychological correlates of obesity remain under controversy. As eating behaviors and dieting history have been previously related to obesity status, these dietary variables may contribute to identify overweight and obese individuals who are at higher risk of having an impaired psychological well-being. OBJECTIVE: The main purpose of this cross-sectional study was to verify the hypothesis of a relationship between weight status and psychological well-being, and to examine whether cognitive dietary restraint, disinhibition, susceptibility to hunger and dieting history could be related to psychological well-being. DESIGN AND SUBJECTS: In a sample of 101 postmenopausal women, we performed anthropometric measurements (weight, height and body mass index (BMI)), and measured psychological well-being (PER Questionnaire). The Three-Factor Eating Questionnaire (TFEQ) and a questionnaire about dieting history (dieters: had already been on a diet; non-dieters: had never been on a diet) were also administrated. RESULTS: A trend for a significant relationship was observed between BMI and psychological well-being (r=-0.17; P=0.08). Significant negative relationships were observed for disinhibition, susceptibility to hunger and all their subscales with psychological well-being (-0.28

Muscle adiposity and body fat distribution in type 1 and type 2 diabetes: varying relationships according to diabetes type.

OBJECTIVE: To compare the relationships between markers of total and regional adiposity with muscle fat infiltration in type 1 diabetic and type 2 diabetic subjects and their respective nondiabetic controls, and to document these relationships in type 1 diabetic subjects. DESIGN: Cross-sectional study. SUBJECTS: In total, 86 healthy, with type 1 diabetes, type 2 diabetes or control subjects. Each diabetic group was matched for age, sex and body mass index with its respective nondiabetic control group. MEASUREMENTS: Measures of body composition (hydrodensitometry), fat distribution (waist circumference, abdominal and mid-thigh computed tomography scans) and blood lipid profiles were assessed. RESULTS: Low attenuation mid-thigh muscle surface correlated similarly with markers of adiposity and body composition in all groups, regardless of diabetes status, except for visceral adipose tissue and waist circumference. Indeed, relationships between visceral adiposity and muscle adiposity were significantly stronger in type 2 vs type 1 diabetic subjects (P<0.05 for comparison of slopes). In addition, in well-controlled type 1 diabetic subjects (mean HbA(1c) of 6.8%), daily insulin requirements tended to correlate with low attenuation mid-thigh muscle surface, a specific component of fat-rich muscle (r=0.36, P=0.08), but not with glycemic control (HbA(1c)). CONCLUSION: This study suggests that the relationship of central adiposity and muscle adiposity is modulated by diabetes status and is stronger in the insulin resistant diabetes type (type 2 diabetes). In well-controlled nonobese type 1 diabetic subjects, the relationship between muscle fat accumulation and insulin sensitivity was also maintained.

Is early and late post-meal exercise so different in type 1 diabetic lispro users?

To compare blood glucose (BG) responses during a 60 min moderate intensity exercise session performed in early or late postprandial periods. Nine generally well-controlled (HbA(1c): 7.3+/-0.1%) type 1 diabetic patients performed, at least one week apart, two exercise sessions, 60 (early exercise) and 180 min (late exercise) after a standardized breakfast. All subjects were using Humulin N (N) and Humalog (Lispro, LI) insulin. During exercise, the overall decrease in BG was 4.8+/-0.6 mmol/l and 3.6+/-0.8 mmol/l in early and late exercise, respectively (P=0.051). To prevent hypoglycemia, a dextrose infusion was initiated when BG reached 5 mmol/l. The quantity of dextrose infused was 6.2+/-3.0 g and 10.5+/-3.2g in early and late exercise, respectively (NS). The time free of dextrose infusion during exercise was 41.2+/-7.8 min and 31.7+/-7.5 min in early and late exercise, respectively (NS). In N-LI users, overall drop in BG during exercise tends to be greater in the early postprandial period. However, early and late exercise present similar quantity of dextrose infused and time free of dextrose infusion. Consequently, the similar risk of exercise-induced hypoglycemia suggests similar precautions in either exercise times.

Physical activity barriers in diabetes: development and validation of a new scale.

To develop and validate a questionnaire measuring perceived Barriers to Physical Activity in Diabetes (type 1) or BAPAD1. Initially, an open-ended questionnaire was filled by 36 patients. The modal accessible beliefs obtained on this pilot study were analysed and a scale composed of 12 items (BAPAD1) was developed and validated. Seventy-four type 1 diabetic patients filled the BAPAD1 scale. Cronbach alpha coefficient was 0.85 and the correlation between the test-retest scores was 0.84, both indicating adequate reliability of the barriers scale. Each item of BAPAD1 scale displayed very good item characteristic curve except for item 12, which was withdrawn. The test reliability curve indicated that the BAPAD1 scale is informative (value>or=0.82) at all levels of perceived barriers toward physical activity. Moreover, among diabetic-related items, the risk of hypoglycemia showed a particularly good item characteristic curve. In summary, the BAPAD1 scale presents excellent psychometric proprieties and among diabetic-related items, the risk of hypoglycemia should be considered as a significant target to overcome in order to increase physical activity. This new validated tool should be useful in identifying the most salient barriers toward the practice of physical activity and thus, permit more focused intervention in order to overcome those barriers.

Genome-wide linkage scans for prediabetes phenotypes in response to 20 weeks of endurance exercise training in non-diabetic whites and blacks: the HERITAGE Family Study.

AIMS/HYPOTHESIS: Impaired insulin secretion, insulin action, insulin-independent glucose effectiveness, glucose tolerance and the associated abnormalities in insulin and glucose metabolism phenotypes are precursors of type 2 diabetes. Genome-wide multipoint variance component linkage scans were carried out using 654 markers to identify quantitative trait loci for insulin sensitivity, acute insulin response to glucose, disposition index and glucose effectiveness training responses in whites and blacks in the HERITAGE Family Study. METHODS: These phenotypes were obtained from an IVGTT with the minimal model. The distributions of insulin sensitivity, acute insulin response to glucose and disposition index training responses (post-training minus baseline) were approximately normalised using a square-root transformation. All phenotypes were adjusted for the effects of age, BMI and their respective baseline values within sex and generation by race prior to linkage scans. RESULTS: In blacks, a promising linkage with a maximum lod score of 3.1 on 19q (54-62 Mb) for glucose effectiveness training response was found. Six interesting linkages with lod scores of at least 1.0 were found for disposition index training response in whites. They included 1p (30 Mb), 3q (152 Mb), 6p (23-42 Mb), 7q (95-96 Mb), 10p (15 Mb) and 12q (119-126 Mb). CONCLUSIONS/INTERPRETATION: Quantitative trait loci for 20 weeks of endurance exercise training responses in insulin action and glucose metabolism phenotypes were found on chromosome 19q as well as 6p and 7q, with nominal (6p, 7q) but consistent (6p) linkages across the races.

High normal 2-hour plasma glucose is associated with insulin sensitivity and secretion that may predispose to type 2 diabetes.

AIMS/HYPOTHESIS: The aim of this study was to evaluate differences in insulin sensitivity, insulin secretion and risk factors for cardiovascular disease between subjects with a 2-h plasma glucose (2hPG) level within the normal range (NPG) and subjects with IGT, following a 75-g OGTT. We also aimed to determine the respective contributions made by 2hPG and fasting plasma glucose to the metabolic risk profile. METHODS: We compared cardiovascular risk factors and insulin sensitivity and insulin secretion by using several indices calculated using measurements obtained during an OGTT. Subjects (n=643, age 18-71 years) were participants in the Quebec Family Study and were categorised according to 2hPG as having low NPG (2hPG <5.6 mmol/l, the group median for normal values), high NPG (2hPG 5.6-7.7 mmol/l) or IGT (2hPG 7.8-11.0 mmol/l). Subjects with type 2 diabetes were excluded from all analyses. RESULTS: Beta cell function and insulin sensitivity progressively decreased with increasing 2hPG. Compared with subjects with low NPG, subjects with high NPG were more insulin-resistant (p<0.05) and had reduced insulin secretion (adjusted for insulin resistance) (p<0.001). They also had higher plasma triglyceride concentrations (p<0.01) and cholesterol:HDL cholesterol ratios (p<0.05). These differences remained even after adjustment for age, sex, BMI and waist circumference. Multivariate analyses showed that 2hPG was closely associated with risk factors for diabetes and with cardiovascular variables, including triglycerides (p<0.0001) and apolipoprotein B (p<0.01). CONCLUSIONS/INTERPRETATION: These results show that deteriorations in glucose-insulin metabolism, which may predispose individuals to type 2 diabetes and cardiovascular disease, are already present in subjects with 2hPG concentrations within the high normal range. Independently of obesity, 2hPG was found to explain, in part, the variance observed in cardiovascular and diabetes risk factors. In addition, elevated 2hPG was associated with metabolic alterations that appear to be the most detrimental to metabolic health. Thus, 2hPG values within the high normal range may be an important marker for the identification of people at risk of complications related to type 2 diabetes.

Impaired fasting glucose vs. glucose intolerance in pre-menopausal women: distinct metabolic entities and cardiovascular disease risk?

BACKGROUND: Impaired glucose tolerance (IGT) is associated with an increased cardiovascular disease risk. Less is known about cardiovascular disease risk among subjects with impaired fasting glucose (IFG) or with combined IFG and IGT. AIMS: To compare body composition, body fat distribution, plasma glucose-insulin homeostasis and plasma lipid-lipoprotein profile between pre-menopausal women having either a normal glucose tolerance (NGT), isolated IFG, isolated IGT or combined IFG and IGT. METHODS: Three hundred and thirty-four women with NGT, 11 women with IFG, 35 women with IGT and 10 women with both IFG and IGT were studied. RESULTS: Women with IFG were characterized by a higher visceral adipose tissue (AT) accumulation than women with NGT (P < 0.05). Also, they were characterized by a higher subcutaneous AT area and by higher body fat mass than NGT and IGT women (P < 0.05). However, their lipid-lipoprotein profile was comparable with that of NGT women, except for reduced HDL-cholesterol concentrations (P < 0.05). After adjustment for visceral AT, women with IFG had lower total cholesterol, LDL-cholesterol and apolipoprotein B (apoB) levels than the three other groups. They also had lower HDL(2)-cholesterol than NGT women and lower total cholesterol/HDL-cholesterol ratio than IGT women. Women with IGT showed higher triglyceride and apoB concentrations and a higher total cholesterol/HDL-cholesterol ratio than women with NGT (P < 0.05). Overall, women with combined IFG and IGT showed body fatness characteristics and alterations in their metabolic risk profile which were essentially similar to women with isolated IGT. CONCLUSIONS: These results indicate that there are significant differences in anthropometric and metabolic variables between pre-menopausal women with IFG vs. IGT and that the association between body fatness-body fat distribution indices and the metabolic profile may differ between IFG and IGT women.