PubMed Health⌕ Search

Biomedical subjects

R J Sigal

Publications and source records attributed to R J Sigal.

18 recordsLinked to original sources
PubMed2006

Impacts of diabetes and hypertension on the risk of hospitalization among less educated people.

Coexisting hypertension increases the morbidity and mortality associated with diabetes, and may be more so in less educated people. We analysed data from 49 904 Canadians 40-64 years of age who participated in the Canadian Community Health Survey, 2000-2001. Multiple classification analysis was used to adjust for covariates. Population weight and design effect of the survey were taken into account in the analysis. The association between hypertension and hospitalization varied according to diabetes and education. The adjusted difference in hospitalization incidence attributable to hypertension was significantly higher for the lower education group than the higher education group, and such a pattern tended to be more pronounced among diabetic people. The adjusted incidence difference attributable to hypertension was higher in the diabetic group (8.8, 95% confidence interval (CI): 4.6, 13.0%) than in the non-diabetic group (4.6, 95% CI: 3.6, 5.6%) for people with low education, but was similar for those with well-educated people. Possible reasons for the modifying effect of education on the relationship among hypertension, diabetes and hospitalization were discussed.

Adult↗
PubMed2006

Association between diabetes and depression: Sex and age differences.

OBJECTIVE: To examine the association between diabetes and the prevalence of depression in different sex and age groups by analysing the cross-sectional data from the National Population Health Survey, conducted in Canada in 1996-1997. STUDY DESIGN: A total of 53072 people aged 20-64 years were included in the analysis. Depression was defined as depression scale 5, based on the Composite International Diagnostic Interview Short-Form (CIDI-SF). Respondents who answered the following question affirmatively were considered to have diabetes: 'do you have diabetes diagnosed by a health professional?'. METHODS: A multiple logistic regression model was used to adjust for potential confounding effects, and a bootstrap procedure was used to take sampling weights and design effects into account. RESULTS: The prevalence of diabetes was much higher in people aged 40-64 years than in people aged 20-39 years (men: 4.7% vs. 0.5%; women: 3.5% vs. 0.8%, respectively). In contrast, people aged 20-39 years had a slightly higher prevalence of depression than those aged 40-64 years (men: 3.1% vs. 2.9%; women: 6.6% vs. 5.4%, respectively). Diabetes was significantly associated with depression in women aged 20-39 years (odds ratio [OR]=2.52, 95% confidence interval [CI]=1.19, 5.32), but not in women aged 40-64 years (OR=1.62, and 95% CI=0.65, 4.06). The association was not significant in both age groups in men, but it tended to be stronger in the younger age group. CONCLUSIONS: The data suggest that diabetes is significantly associated with depression, particularly in young adults.

Adult↗
PubMed2005

Influence of Pro12Ala peroxisome proliferator-activated receptor gamma2 polymorphism on glucose response to exercise training in type 2 diabetes.

AIMS/HYPOTHESIS: Exercise training improves glycaemic control in some but not all individuals and little research has been done regarding genetic impact on the exercise training response in type 2 diabetes. The purpose of this study was to investigate the influence of the Pro(12)Ala variant of the peroxisome proliferator-activated receptor (PPAR) gamma2 gene on changes in fasting plasma glucose in response to exercise training. METHODS: The study population comprised 139 sedentary type 2 diabetic patients (age: 54.4+/-7.2; HbA(1)c: 7.7+/-0.9%) who completed 3 months of supervised exercise training. The primary outcome variable in our analysis was the post-intervention change in blood glucose. Other assessments included measures of body composition, insulin sensitivity indices and maximal oxygen uptake (VO(2max)). RESULTS: The frequency of the Ala allele was 8.3% and the genotypes were in Hardy-Weinberg equilibrium. At baseline, neither body composition variables (weight, BMI, waist circumference), glucose homeostasis variables (glucose, insulin, HbA(1)c, homeostasis model assessment method) nor VO(2max) were different between genotypes (wild-type: Pro(12)Pro n=117, Ala carriers: X(12)Ala n=22). The exercise-training intervention led to similar improvements in body composition and glucose homeostasis variables in both genotype groups (p<0.05). The change in fasting plasma glucose was significantly different between PPARgamma2 genotypes (-1.66 mmol/l vs -0.54 mmol/l, Ala carriers and wild-type, respectively) (p=0.034 unadjusted and p=0.089 including baseline glucose) and the significant association between genotype and glucose response remained after adjusting for statistically significant predictors (age, changes in insulin and BMI [p=0.015]) and including baseline glucose, insulin and BMI (p=0.031). CONCLUSIONS/INTERPRETATION: These data suggest that the Pro(12)Ala polymorphism may influence the glycaemic response to exercise in type 2 diabetes.

Adult↗
PubMed2003

Meta-analysis of the effect of structured exercise training on cardiorespiratory fitness in Type 2 diabetes mellitus.

AIMS/HYPOTHESIS: Low cardiorespiratory fitness is a powerful and independent predictor of mortality in people with diabetes. Several studies have examined the effects of exercise on cardiorespiratory fitness in Type 2 diabetic individuals. However, these studies had relatively small sample sizes and highly variable results. Therefore the aim of this study was to systematically review and quantify the effects of exercise on cardiorespiratory fitness in Type 2 diabetic individuals. METHODS: MEDLINE, EMBASE, and four other databases were searched up to March 2002 for randomized, controlled trials evaluating effects of structured aerobic exercise interventions of 8 weeks or more on cardiorespiratory fitness in adults with Type 2 diabetes. Cardiorespiratory fitness was defined as maximal oxygen uptake (VO(2max)) during a maximal exercise test. RESULTS: Seven studies, presenting data for nine randomized trials comparing exercise and control groups (overall n=266), met the inclusion criteria. Mean exercise characteristics were as follows: 3.4 sessions per week, 49 min per session for 20 weeks. Exercise intensity ranged from 50% to 75% of VO(2max). There was an 11.8% increase in VO(2max) in the exercise group and a 1.0% decrease in the control group (post intervention standardized mean difference =0.53, p<0.003). Studies with higher exercise intensities tended to produce larger improvements in VO(2max). Exercise intensity predicted post-intervention weighted mean difference in HbA(1c) (r=-0.91, p=0.002) to a larger extent than did exercise volume (r=-0.46, p=0.26). CONCLUSIONS/INTERPRETATION: Regular exercise has a statistically and clinically significant effect on VO(2max) in Type 2 diabetic individuals. Higher intensity exercise could have additional benefits on cardiorespiratory fitness and HbA(1c).

Databases, Factual↗
PubMed2001

Effects of exercise on glycemic control and body mass in type 2 diabetes mellitus: a meta-analysis of controlled clinical trials.

CONTEXT: Exercise is widely perceived to be beneficial for glycemic control and weight loss in patients with type 2 diabetes. However, clinical trials on the effects of exercise in patients with type 2 diabetes have had small sample sizes and conflicting results. OBJECTIVE: To systematically review and quantify the effect of exercise on glycosylated hemoglobin (HbA(1c)) and body mass in patients with type 2 diabetes. DATA SOURCES: Database searches of MEDLINE, EMBASE, Sport Discuss, Health Star, Dissertation Abstracts, and the Cochrane Controlled Trials Register for the period up to and including December 2000. Additional data sources included bibliographies of textbooks and articles identified by the database searches. STUDY SELECTION: We selected studies that evaluated the effects of exercise interventions (duration >/=8 weeks) in adults with type 2 diabetes. Fourteen (11 randomized and 3 nonrandomized) controlled trials were included. Studies that included drug cointerventions were excluded. DATA EXTRACTION: Two reviewers independently extracted baseline and postintervention means and SDs for the intervention and control groups. The characteristics of the exercise interventions and the methodological quality of the trials were also extracted. DATA SYNTHESIS: Twelve aerobic training studies (mean [SD], 3.4 [0.9] times/week for 18 [15] weeks) and 2 resistance training studies (mean [SD], 10 [0.7] exercises, 2.5 [0.7] sets, 13 [0.7] repetitions, 2.5 [0.4] times/week for 15 [10] weeks) were included in the analyses. The weighted mean postintervention HbA(1c) was lower in the exercise groups compared with the control groups (7.65% vs 8.31%; weighted mean difference, -0.66%; P<.001). The difference in postintervention body mass between exercise groups and control groups was not significant (83.02 kg vs 82.48 kg; weighted mean difference, 0.54; P =.76). CONCLUSION: Exercise training reduces HbA(1c) by an amount that should decrease the risk of diabetic complications, but no significantly greater change in body mass was found when exercise groups were compared with control groups.

Adult↗
PubMed2000

Glucoregulation during and after intense exercise: effects of alpha-adrenergic blockade.

In intense exercise (>80% maximal oxygen consumption [VO2 max]), the 7- to 8-fold increase in glucose production (Ra) is tightly correlated with the greater than 14-fold increase in plasma norepinephrine (NE) and epinephrine (EPI). To distinguish the relative roles of alpha- and beta-adrenergic receptors, the responses of 12 control (C) lean, healthy, fit young male subjects to 87% VO2 max cycle ergometer exercise were compared with those of 7 subjects (at 83% VO2max) receiving intravenous phentolamine (Ph). The Ph group received a 70-microg/kg bolus and then 7 microg/kg/min from -30 minutes, during exercise and for 60 minutes of recovery. The data were analyzed by comparing exercise responses to exhaustion in Ph subjects (11.4 +/- 0.6 min) with those at both 12 minutes and at exhaustion in C subjects (14.6 +/- 0.3 min) and during recovery. There were no significant differences between groups in the plasma glucose response during exercise, but values were higher in C versus Ph subjects during the first 40 minutes of postexercise "recovery." The Ra response during the first 12 minutes of exercise was not different by repeated-measures ANOVA, reaching 10.6 +/- 1.3 mg/kg/min in C and 9.6 +/- 1.5 in Ph subjects at 12 minutes. However, in C subjects, Ra increased significantly to 14.1 +/- 1.2 mg/kg/min by exhaustion, and remained higher versus Ph subjects until 15 minutes of recovery. The Rd during recovery was not different between groups; thus, the higher Ra in C subjects in early recovery was responsible for the greater hyperglycemia observed in C subjects. Ph subjects showed a more rapid, marked increment (P = .002) in both plasma NE (to 64 v38 nmol/L) and EPI at exhaustion, and catecholamine concentrations remained higher in Ph versus C subjects during recovery. Whereas plasma insulin (IRI) declined in the C group, it increased 3-fold (P = .001) in the Ph group during exercise and until 15 minutes of recovery. Ph had no effect on glucagon (IRG). Thus, the glucagon to insulin ratio decreased in Ph subjects from baseline levels during exercise and early recovery, but increased in C subjects. The increase in Ra among Ph subjects despite the decrease in the glucagon to insulin ratio supports our earlier evidence that these hormones are not principal regulators of the Ra in intense exercise. The shorter time to exhaustion and markedly higher catecholamine levels in Ph subjects limited our ability to isolate the effects of alpha-adrenergic receptors on the Ra.alpha-Adrenergic receptors appear to have little influence on the Rd.

Adrenergic alpha-Antagonists↗
PubMed1999

Walking compared with vigorous physical activity and risk of type 2 diabetes in women: a prospective study.

CONTEXT: Although many studies suggest that physical activity may reduce risk of type 2 diabetes, the role of moderate-intensity activity such as walking is not well understood. OBJECTIVES: To examine the relationship of total physical activity and incidence of type 2 diabetes in women and to compare the benefits of walking vs vigorous activity as predictors of subsequent risk of type 2 diabetes. DESIGN AND SETTING: The Nurses' Health Study, a prospective cohort study that included detailed data for physical activity from women surveyed in 11 US states in 1986, with updates in 1988 and 1992. PARTICIPANTS: A total of 70,102 female nurses aged 40 to 65 years who did not have diabetes, cardiovascular disease, or cancer at baseline (1986). MAIN OUTCOME MEASURE: Risk of type 2 diabetes by quintile of metabolic equivalent task (MET) score, based on time spent per week on each of 8 common physical activities, including walking. RESULTS: During 8 years of follow-up (534, 928 person-years), we documented 1419 incident cases of type 2 diabetes. After adjusting for age, smoking, alcohol use, history of hypertension, history of high cholesterol level, and other covariates, the relative risks (RRs) of developing type 2 diabetes across quintiles of physical activity (least to most) were 1.0, 0.77, 0.75, 0.62, and 0.54 (P for trend <.001); after adjusting for body mass index (BMI), RRs were 1.0, 0.84, 0.87, 0.77, and 0.74 (P for trend = .002). Among women who did not perform vigorous activity, multivariate RRs of type 2 diabetes across quintiles of MET score for walking were 1.0, 0.91,0.73, 0.69, and 0.58 (P for trend <.001). After adjusting for BMI, the trend remained statistically significant (RRs were 1.0, 0.95, 0.80, 0.81, 0.74; P for trend = .01). Faster usual walking pace was independently associated with decreased risk. Equivalent energy expenditures from walking and vigorous activity resulted in comparable magnitudes of risk reduction. CONCLUSIONS: Our data suggest that greater physical activity level is associated with substantial reduction in risk of type 2 diabetes, including physical activity of moderate intensity and duration.

Adult↗
PubMed1999

Glucoregulation during and after intense exercise: effects of beta-adrenergic blockade in subjects with type 1 diabetes mellitus.

In intense exercise (>80% maximum oxygen uptake) a huge, up to 8-fold increase in glucose production (Ra) is tightly correlated to marked increases in plasma norepinephrine (NE) and epinephrine. Both Ra and glucose uptake (Rd) are enhanced, not reduced, during beta-adrenergic blockade in normal subjects. Beta-blockade also caused a greater fall in immunoreactive insulin (IRI) during exercise, which could, in turn, have increased Ra directly or via an increased glucagon/insulin ratio. To control for adrenergic effects on endogenous insulin secretion, we tested type 1 diabetic subjects (DM) made euglycemic by overnight i.v. insulin that was kept constant in rate during and after exercise. Their responses to postabsorptive cycle ergometer exercise at 85-87% maximum oxygen uptake for approximately 14 min were compared to those of similar male control (CP) subjects. Six DM and seven CP subjects received i.v. 150 microg/kg propranolol over 20 min, then 80 microg/kg x min from -30 min, during exercise and for 60 min during recovery. Plasma glucose increased from similar resting values to peaks of 6.8 mmol/L in DM and 6.5 mmol/L in CP, then returned to resting values in CP within 20 min, but in DM, remained higher than in CP from 8-60 min (P = 0.049). Ra rose rapidly until exhaustion, to 13.3 mg/kg x min in CP and 11.6 in DM (P = NS). Ra declined rapidly in recovery, although somewhat more slowly in DM (P = 0.013 from 2-15 min). The Rd increased to 10.6 in CP and 9.2 mg/kg x min in DM (P = NS), then declined similarly in early recovery, but remained higher in CP from 50-100 min (P = 0.05). The rises in plasma glucose during exercise in both groups were thus due to the increments in Rd less than those in Ra. The higher recovery glucose in DM was due to the slower decline in Ra and the lower Rd in later recovery. IRI was higher in DM than in CP before exercise (P = 0.011), and whereas it decreased in CP (P < 0.05), it increased approximately 2-fold in DM, thus being higher throughout exercise (P = 0.003). The glucagon/insulin ratio was unchanged in DM, but increased in CP during exercise (P = 0.002). NE showed a rapid, marked increment during exercise to peak values of 23.7 nmol/L in CP and 25.7 nmol/L in DM (P = NS), and epinephrine showed parallel responses. Both correlated significantly with the Ra responses. In summary, the Ra responses of both DM and CP during exercise were greater than those of control unblocked subjects (previously reported) despite higher IRI (all exogenous) in DM. This suggests an important contribution of direct alpha-adrenergic stimulation to this Ra effect.

Adolescent↗
PubMed1998

Glucose infusion partially attenuates glucose production and increases uptake during intense exercise.

Glucose infusion can prevent the increase in glucose production (Ra) and increase glucose uptake (Rd) during exercise of moderate intensity. We postulated that 1) because in postabsorptive intense exercise (>80% maximal O2 uptake) the eightfold increase in Ra may be mediated by catecholamines rather than by glucagon and insulin, exogenous glucose infusion would not prevent the Ra increment, and 2) such infusion would cause greater Rd. Fit young men were exercised at >85% maximal O2 uptake for 14 min in the postabsorptive state [controls (Con), n = 12] or at minute 210 of a 285-min glucose infusion. In seven subjects, the infusion was constant (CI; 4 mg . kg-1 . min-1), and in seven subjects it was varied (VI) to mimic the exercise Ra response in Con. Although glucose suppressed Ra to zero (with glycemia approximately 6 mM and insulin approximately 150 pM), an endogenous Ra response to exercise occurred, to peak increments two-thirds those in Con, in both CI and VI. Glucagon was unchanged, and very small increases in the glucagon-to-insulin ratio occurred in all three groups. Catecholamine responses were similar in all three groups, and correlation coefficients of Ra with plasma norepinephrine and epinephrine were significant in all. In all CI and VI, Rd at rest was 2x Con, increased earlier in exercise, and was higher for the 1 h of recovery with glucose infusion. Thus the Ra response was only partly attenuated, and the catecholamines are likely to be the regulators. This suggests that an acute endogenous Ra rise is possible even in the postprandial state. Furthermore, the fact that more circulating glucose is used by muscle during exercise and early recovery suggests that muscle glycogen is spared.

Adolescent↗
PubMed1997

Effect of glycemic control on the kinetics of whole-body protein metabolism in obese subjects with non-insulin-dependent diabetes mellitus during iso- and hypoenergetic feeding.

We postulated whether interventions capable of restoring euglycemia would correct whole-body protein metabolism, shown previously to be elevated in hyperglycemic persons with non-insulin-dependent diabetes (NIDDM). The kinetics of protein metabolism were estimated in obese subjects with NIDDM in the hyper- and normoglycemic states during isoenergetic feeding and in the normoglycemic state induced by 4 wk of a very-low-energy diet (VLED) with constant protein intake. Seven NIDDM subjects [three males and four females with a body mass index (in kg/m2) of 39 +/- 2] were given a weight-maintaining, liquid formula providing 95 g protein/d for 15 d, followed in six subjects (two males and four females) for 27 d by a diet providing 1.7 MJ, 93 g protein derived from casein-soy, 13 g carbohydrate, 2 g fat, multivitamins and minerals, and a potassium bicarbonate supplement (32 mmol) per day. Exogenous insulin was given to achieve normoglycemia during the first 8 d of isoenergetic feeding. On days 6-8, 12-14, and 25-27, nitrogen flux rate was calculated from the urine [15N]urea enrichment by using the 60-h oral [15N]glycine method to obtain "integrated" feeding and fasting values. Rates of synthesis and breakdown were calculated from nitrogen flux. During isoenergetic feeding, normoglycemia was associated with more positive nitrogen balance (2.6 +/- 0.5 compared with -0.6 +/- 0.6 g N/d, P < 0.05); 18-23% lower nitrogen flux, and synthesis and breakdown rates (P < 0.05), and a 3% decrease in resting energy expenditure (P < 0.05). During the VLED, euglycemia was achieved but nitrogen balance, although it became less negative with time, never reached equilibrium. This was associated with significant (P < 0.05) decreases in the synthesis rate, resulting in net protein losses. Thus, the altered protein metabolism in moderately hyperglycemic NIDDM subjects was improved with exogenous insulin in doses sufficient to restore normoglycemia in the isoenergetic fed state, but it remained abnormal with a reduced non-protein energy intake. This suggests that protein metabolism is more sensitive to insulinization than was thought previously.

Adult↗
PubMed1997

Acute postchallenge hyperinsulinemia predicts weight gain: a prospective study.

The relationships of insulin secretion and insulin action to body weight are incompletely understood. Obesity is associated with reduced sensitivity to insulin and high fasting and postprandial serum insulin levels. However, it is unknown whether insulin secretion rises to compensate for insulin resistance or high insulin secretion promotes body weight gain and the development of insulin resistance. To shed light on this question, we examined weight gain over an interval of 16.7 +/- 3.9 years (mean +/- SD) in 107 glucose-tolerant offspring (48 men, 59 women) of two parents with NIDDM. The offspring had a baseline intravenous glucose tolerance test, at which time they were aged 32.9 +/- 9.7 years, and only those who did not develop diabetes during the follow-up period were included. We estimated insulin sensitivity with the insulin sensitivity index from Bergman's minimal model of glucose disposal and acute insulin secretion from the incremental area under the insulin curve in the first 10 min of the intravenous glucose tolerance test. Weight-gain rate (g/year) was defined as the regression slope of each subject's body weight over time. High acute insulin secretion, young age, and low baseline percent ideal body weight (IBW) were each associated with a high rate of weight gain. After adjustment for differences in age and IBW, statistically significant effects of insulin sensitivity (P = 0.05) as well as acute insulin secretion (P = 0.001) were obtained. To estimate the effects of acute insulin secretion and insulin sensitivity on the average rate of weight gain (adjusting for age and IBW), the study group was stratified into four subgroups by dividing it at the medians of these two variables. Among those with low acute insulin secretion, weight-gain rate was the same regardless of whether insulin sensitivity was low or high (176 and 152 g/year, respectively). Among those with high acute insulin secretion, mean weight-gain rate was still rather low in those with low insulin sensitivity (271 g/year), but it was quite high in those with high insulin sensitivity (672 g/year; significantly higher than in all other subgroups). Therefore a high first-phase insulin response to intravenous glucose is a risk factor for long-term weight gain, and this effect is particularly manifested in insulin-sensitive individuals.

Adolescent↗
PubMed1996

Codon 972 polymorphism in the insulin receptor substrate-1 gene, obesity, and risk of noninsulin-dependent diabetes mellitus.

Because of the role of insulin receptor substrate-1 in insulin action, the insulin receptor substrate-1 gene is a candidate gene for noninsulin-dependent diabetes mellitus (NIDDM). Modest associations between NIDDM and a GGG-->AGG single base substitution (corresponding to a glycine-->arginine amino acid substitution) in codon 972 of the gene have been found, but none reached statistical significance. To examine further how large a proportion of NIDDM cases could be caused by the mutation, we performed a stratified analysis combining the results from the 6 earlier studies and those from our panel of 192 unrelated NIDDM subjects and 104 healthy controls. In addition, we looked for a possibility that the codon 972 mutation plays a role only in the presence of certain conditions. Genomic DNA samples obtained from NIDDM cases and healthy controls were genotyped using a PCR-restriction fragment length polymorphism protocol modified for genomic DNA. The GGG-->AGG substitution was found in 5.7% of the diabetic subjects (11 of 192) and 6.9% of the controls (7 of 104). The difference between groups was not statistically significant, and it was not different from the results of other studies. The Mantel-Haenszel summary odds ratio across all studies was 1.49 (P < 0.05; 95% confidence intervals, 1.01-2.2). This summary odds ratio is consistent with a small proportion of NIDDM cases (approximately 3%) being caused by the mutation. Exploratory subgroup analyses on our panel suggested a clustering of NIDDM, the codon 972 mutation, and overweight, raising the hypothesis that the mutation may predispose to NIDDM only in the presence of excess body weight.

Adult↗
PubMed1996

The roles of catecholamines in glucoregulation in intense exercise as defined by the islet cell clamp technique.

Exercise at > 85% VO2max causes the greatest known physiological increases in glucose production rates (Ra). To define the relative roles of catecholamine versus glucagon/insulin responses in stimulating Ra, normal subjects in the postabsorptive state exercised at 87 +/- 2% VO2max during an islet cell clamp (IC): intravenous octreotide (somatostatin analog), 30 ng.kg-1.min-1; glucagon, 0.8 ng.kg-1.min-1; growth hormone, 10 ng.kg-1.min-1; and insulin adjusted to achieve euglycemia, then constant 56 +/- 7 min before exercise. Seven control subjects exercised without an IC. In four subjects (IC-1) with hormone infusions held constant during exercise, plasma insulin rose 76% and glucagon 35%, perhaps because of altered hemodynamics. In seven subjects (IC-2), hormone infusions were decreased stepwise during exercise and returned stepwise to initial rates during early recovery. Ra increased sixfold in control and both IC groups. Plasma norepinephrine and epinephrine likewise increased > 12-fold with no differences among groups; both catecholamines correlated closely with Ra. Because mixed venous blood plasma insulin declined and glucagon did not change in control subjects, the glucagon-to-insulin ratio increased from 0.20 to 0.26 (P = 0.02). In IC subjects, plasma insulin increased and glucagon was either constant (IC-2) or increased less than insulin, resulting in nonsignificant declines in the immunoreactive glucose-to-immunoreactive insulin ratio. Although a rise in insulin would have been expected to attenuate the Ra increment, this effect was overridden. The strong correlations of Ra with catecholamines and the similar Ra responses despite divergent glucagon-to-insulin responses are consistent with the primacy of catecholamines in regulation of Ra in intense exercise.

Adult↗
PubMed1996

Natural history of impaired glucose tolerance: follow-up at Joslin Clinic.

The goal of this study was to examine follow-up data on the offspring of two parents with NIDDM who have IGT to identify predictors of progression to NIDDM. The study group consisted of 80 individuals with IGT (WHO criteria), 28 of whom had IGT at baseline, and 52 who developed it during follow-up. Both an oral glucose tolerance test (OGTT) and an intravenous glucose tolerance test (IVGTT) were performed at baseline. After a median follow-up interval of 8 years, 35% had progressed to NIDDM, 37% had reverted to normal glucose tolerance, and 29% still had IGT. Those who progressed were younger and more obese than non-progressors. Glucose and insulin values from the OGTT that established the diagnosis of IGT were analysed by multiple logistic regression to determine which time points best discriminated between progressors and non-progressors. High insulin, but not glucose, values at 0 and 120 min distinguished progressors from non-progressors. Values at other sample times that were significantly different (p < 0.05) in progressors were: higher glucose values at 30, 45, and 60 min and higher insulin values at 90 and 180 min. Multiple logistic regression analysis of Bergman's minimal model parameters obtained from the IVGTTs performed at baseline demonstrated that, once IGT is established, low acute phase insulin secretion as well as low insulin sensitivity are significant predictors of progression to NIDDM.

Adult↗
PubMed1994

Glucoregulation during and after intense exercise: effects of beta-blockade.

To define the roles of beta- and alpha-adrenergic receptors in intense exercise, 17 lean healthy fit young males underwent 13.6 +/- 0.2 (+/-SE) min of cycle ergometer exercise: 6 at 100% maximum oxygen uptake (VO2max; MAX), 7 at their maximum possible (87 +/- 2.3%) during iv propranolol (P; 150 micrograms/kg bolus 30 min preexercise, then 80 micrograms/kg.min), and 7 (including 3 of the P subjects) at 87% VO2max (C) as controls for P. Plasma glucose increased from similar resting values to a peak in the early recovery period at 7.2 +/- 0.44 in MAX and 6.8 +/- 0.37 in P, but only 5.2 +/- 0.3 mmol/L in C. The rate of glucose appearance (Ra) rose about 8-fold in both MAX and P, but only 4-fold in C (P = 0.001). The rate of glucose disappearance (Rd) increased 4-fold in MAX, 5.5-fold in P, and 3-fold in C (P = 0.001). Plasma insulin declined during exercise (P < 0.05) in MAX and P, but not in C, whereas plasma glucagon increased modestly in all groups. The mean peak plasma norepinephrine level was 36.3 +/- 4.5 in MAX, 20.2 +/- 3.4 in P, and 15.2 +/- 2.9 nmol/L in C (P = 0.002); epinephrine reached 7141 +/- 1790 in MAX and 5605 +/- 1532 in P (P = NS), but only 1715 +/- 344 pmol/L in C (P = 0.03). Therefore, 1) an "unmasked" alpha-adrenergic effect, directly and/or via an altered glucagon/insulin ratio, probably contributed to increased Ra with P treatment; and 2) the marked facilitation of the increase in Rd with P supports a major role for beta-adrenergic restraint of Rd at this exercise intensity.

Adolescent↗
PubMed1994

Hyperinsulinemia prevents prolonged hyperglycemia after intense exercise in insulin-dependent diabetic subjects.

Hyperglycemia with accompanying hyperinsulinemia occurs after brief, greater than 85% maximum oxygen consumption exercise to exhaustion in normal subjects and persists up to 60 min of recovery. To determine the importance of endogenous insulin secretion during and after intense exercise, responses to exercise of lean fit male post-absorptive insulin-dependent diabetes mellitus (IDDM) subjects, aged 18-34 yr, were compared with those of control subjects (C; n = 6). Three iv insulin protocols were employed: hyperglycemic (HG; n = 7) and euglycemic (EG1; n = 6) with constant insulin infusion, and euglycemic with doubled insulin infusion during recovery (EG2; n = 6). Overnight iv insulin was adjusted to achieve prolonged euglycemia (5.4 +/- 0.3 mmol/L) or hyperglycemia (8.6 +/- 0.3 mmol/L) before exercise. This allowed for comparisons between HG and EG1 (constant infusion) and between C and EG2 (to approximate physiological hyperinsulinemia by doubling the infusion rates at exhaustion for 56 +/- 7 min during recovery). Subjects exercised to 89-98% of their individual maximum oxygen consumption for 12.8 +/- 0.3 min. Glycemia increased to maximum values at 6 min of recovery (9.8 +/- 0.5 in HG, 6.9 +/- 0.4 in EG1, 7.3 +/- 0.3 in EG2, and 6.9 +/- 0.4 mmol/L in C). Whereas in EG2 and C, glucose returned to resting values in 50-80 min, it remained elevated at 120 min recovery in HG and EG1. During exercise, [3-3H]-glucose-determined glucose production increased markedly and exceeded disappearance in all groups, but less so in the HG subjects than in the other groups. An early recovery decline in glucose production did not differ among groups, but MCR (rate of glucose disappearance/glycemia) were markedly lower in HG and EG1, in whom plasma free insulin remained unchanged from 15 min of recovery onward (MCR, 1.6-1.9 vs. 2.3-2.8 mL/kg.min in C). Doubling the insulin infusion rate in EG2 restored the MCR response to that of C subjects. In summary, constant insulin infusion is insufficient to prevent prolonged postexercise hyperglycemia in IDDM subjects, even when provided at a rate sufficient to maintain normal resting glycemia and glucose turnover. The finding that increasing the rate of insulin infusion restored plasma glucose to normal in IDDM subjects suggests that the postexercise increase in insulin levels observed in normal subjects is essential to return plasma glucose to resting levels. Therefore, special strategies, differing from those for less strenuous exercise, are required for the management of insulin therapy in IDDM during and after intense exercise.

Adolescent↗