Glycemic index, postprandial glycemia and cardiovascular disease

PURPOSE OF REVIEW: Several lines of evidence indicate that exaggerated postprandial glycemia puts individuals without diabetes at greater risk of developing cardiovascular disease. In large, prospective observational studies, including meta-analyses, higher 120 min post-load blood glucose and glycated hemoglobin (a measure of average blood glucose level over time) independently predict cardiovascular mortality and morbidity in individuals without diabetes. These findings imply that the glycemic nature of dietary carbohydrates may also be relevant. We aim to provide a clearer perspective on how the glycemic impact of carbohydrates may modulate development of cardiovascular disease. RECENT FINDINGS: In ecological studies, average dietary glycemic index (a measure of the postprandial glycemic potential of carbohydrates) and glycemic load (average glycemic index x amount of carbohydrate) predicts coronary infarct and cardiovascular disease risk factors, including HDL cholesterol, triglycerides and C-reactive protein. In short-term intervention studies of overweight and hyperlipidemic patients, low glycemic index diets lead to improvements in cardiovascular disease risk factors, including reduced LDL cholesterol and improved insulin sensitivity, as well as greater body fat loss on energy-restricted diets. Molecular studies indicate that physiological hyperglycemia induces overproduction of superoxide by the mitochondrial electron-transport chain, resulting in inflammatory responses and endothelial dysfunction. SUMMARY: Taken together, the findings suggest that conventional high-carbohydrate diets with their high glycemic index may be suboptimal, particularly in insulin-resistant individuals. Because around one in four adults has impairments in postprandial glucose regulation, the glycemic potential of carbohydrates warrants further investigation in cardiovascular disease prevention.     

Glycemic index of a meal fed before exercise alters substrate use and glucose flux in exercising horses.

In a randomized, balanced, crossover study each of six fit, adult horses ran on a treadmill at 50% of maximal rate of oxygen consumption for 60 min after being denied access to food for 18 h and then 1) fed corn (51.4 kJ/kg digestible energy), or 2) fed an isocaloric amount of alfalfa 2-3 h before exercise, or 3) not fed before exercise. Feeding corn, compared with fasting, resulted in higher plasma glucose and serum insulin and lower serum nonesterified fatty acid concentrations before exercise (P < 0.05) and in lower plasma glucose, serum glycerol, and serum nonesterified fatty acid concentrations and higher skeletal muscle utilization of blood-borne glucose during exercise (P < 0.05). Feeding corn, compared with feeding alfalfa, resulted in higher carbohydrate oxidation and lower lipid oxidation during exercise (P < 0.05). Feeding a soluble carbohydrate-rich meal (corn) to horses before exercise results in increased muscle utilization of blood-borne glucose and carbohydrate oxidation and in decreased lipid oxidation compared with a meal of insoluble carbohydrate (alfalfa) or not feeding. Carbohydrate feedings did not produce a sparing of muscle glycogen compared with fasting.     

Standardized Glycemic Management and Perioperative Glycemic Outcomes in Patients with Diabetes Mellitus who Undergo Same-Day Surgery

ObjectiveTo assess the safety and effectiveness of a standardized glycemic management protocol in patients with diabetes mellitus who undergo same-day surgery.MethodsThe perioperative glycemic management protocol consisted of preoperative instructions and perioperative order sets for management of subcutaneous and intravenous insulin. Patients with known diabetes admitted to same-day surgery during a 10-month period were observed. Patient demographic information and all capillary blood glucose (CBG) values obtained during the sameday surgery visit were collected. Hyperglycemia, defined as a CBG concentration of 200 mg/dL or greater, prompted notification of the attending anesthesiologist. While use of the perioperative order sets was encouraged, the attending anesthesiologist retained the prerogative to treat according to these order sets or their usual care. Physician compliance with the standardized order sets was determined by chart review in the patients who had a documented blood glucose value of 200 mg/dL or greater.ResultsPatients managed with the standardized order sets had greater reductions in CBG values (percentage change, 35 ± 20.5% vs 18 ± 24%, P < .001) and lower postoperative CBG values (186 ± 53 mg/dL vs 208 ± 63 mg/dL, P < .05) than patients who received usual care. No cases of intraoperative or postoperative hypoglycemia (CBG < 70 mg/dL) were observed in either group.ConclusionsA systematic approach to glycemic management that includes instructions for preoperative adjustments to home diabetic medications and order sets for treatment of perioperative hyperglycemia is safe and can be more effective than usual care for ambulatory surgery patients with diabetes. (Endocr Pract. 2011;17:404-411)     

Albumin index in spot urine from outpatients with noninsulin-dependent diabetes mellitus

The albumin index (mg/g . creatinine) was determined in untimed spot urine collected in the early morning from 92 randomly selected outpatients with noninsulin-dependent diabetes mellitus (NIDDM). The patients were divided into three groups: 49 patients with normo-albuminuria (albumin index less than 9.1), 24 with micro-albuminuria (albumin index between 9.1 and 100), and 19 with overt-albuminuria (albumin index over than 100). With diabetic duration, the frequency of the patients with overt-albuminuria was increased, but that with normo-albuminuria was decreased. The patients treated with only a diet almost showed normo-albuminuria. In contrast, micro-and overt-albuminuria were found more frequently in the patients treated with oral hypoglycemic agents or insulin. Micro- and overt-albuminuria were found more frequently in the patients with poor glycemic control than in those with good glycemic control. The urinary albumin index was significantly high in the micro-albuminuric patients with poor glycemic control. Similarly, micro- and overt-albuminuria were found more frequently in the patients associated with diabetic retinopathy or neuropathy than in those without diabetic complications. In addition, overt-albuminuria was found more frequently in the patients with hypertension. The urinary albumin index was significantly high in the overt-albuminuric patients with hypertension. In conclusion, the determination of the albumin index in spot urine may be outpatients with NIDDM.     

Predictors of decrease in ankle-brachial index among patients with diabetes mellitus

Diabet. Med. 29, e304-e307 (2012) ABSTRACT: Aim Screening for peripheral arterial disease, a complication among patients with diabetes, is performed by periodic assessment of ankle-brachial index. We aimed to study the degree of ankle-brachial index change over time and factors associated with significant change. Method We assessed difference between two ankle-brachial index measurements over time in a consecutive series of 82 patients with Type?2 diabetes. All patients had ankle-brachial index >?0.9 but ≤?1.3 for the first measurement, and significant ankle-brachial index decrease was defined as a decrease of >?0.1 in the follow-up measurement compared with the baseline. Results The mean follow-up duration was 27.6 (median 30.0) months. Significant ankle-brachial index decrease was seen in 20.7% of patients, including 5% with follow-up ankle-brachial index of ≤?0.9, consistent with the diagnosis of peripheral arterial disease. After adjusting for age and gender, higher baseline HbA(1c) and serum creatinine levels, increase in follow-up serum LDL cholesterol levels compared with baseline and history of retinopathy were predictors of significant ankle-brachial index decrease. Conclusions Our study suggests that, within two?years, one in five patients with diabetes and a normal ankle-brachial index may have significant progression of peripheral arterial disease. Annual ankle-brachial index assessment and better control of hyperlipidaemia may thus be required for at-risk patients with poor glycaemic control, renal impairment and retinopathy.     

Glycemic Index,Glycemic Load and Mammographic Breast Density: The EPIC Florence Longitudinal Study

A few studies have evaluated the association between diet and mammographic breast density (MBD) and results are inconsistent. MBD, a well-recognized risk factor for breast cancer, has been proposed as a marker of cumulative exposure to hormones and growth factors. Diets with a high glycemic index (GI) or glycemic load (GL) may increase breast cancer risk, via an effect on the insulin-like growth factor axis. We have investigated the association between carbohydrate intake, GI, GL and MBD in a prospective study. We identified a large series of women, in the frame of the EPIC-Florence cohort, with a mammogram taken five years after enrolment, when detailed information on dietary and lifestyle habits and anthropometric measurements had been collected. Mammograms have been retrieved (1,668, 83%) and MBD assessed according to Wolfe’s classification. We compared women with high MBD (P2+DY Wolfe’s categories) with those with low MBD (N1+P1) through logistic models adjusted for age, education, body mass index, menopause, number of children, breast feeding, physical activity, non-alcohol energy, fibers, saturated fat and alcohol. A direct association between GL and high MBD emerged in the highest quintile of intake in comparison with the lowest quintile (OR = 1.73, 95%CI 1.13–2.67, p for trend = 0.048) while no association with glycemic index was evident. These results were confirmed after exclusion of women reporting to be on a diet or affected with diabetes, and when Hormone Replacement Therapy at the date of mammographic examination used to assess MBD was considered. The effect was particularly evident among leaner women, although no interaction was found. A positive association was suggested for increasing simple sugar and total carbohydrates intakes limited to the highest quintiles. In this Italian population we observed an association between glycemic load, total and rapidly absorbed carbohydrates and high MBD. These novel results warrant further investigations.     

Fatty liver index predicts further metabolic deteriorations in women with previous gestational diabetes

Background and Aims

Determinants of fatty liver (FL) might be predictive for further deterioration in insulin resistance (IR) in women with previous gestational diabetes (pGDM). The aim was to evaluate the association between pGDM, FL and future manifestation of type 2 diabetes (T2DM) by a detailed pathophysiological characterization early after pregnancy.

Methods

68 pGDM and 29 healthy controls were included 3–6 months after delivery and underwent specific metabolic assessments: status of IR was determined via oral- and intravenous-glucose-tolerance-tests with analysis of proinflammatory factors and kinetics of free-fatty-acids (FFA). According to the fatty-liver-index (FLI), pGDMs were categorized into three groups with low (FLI≤20), intermediate (20ResultsFL was strongly associated with IR in pGDM. pGDM with FLI≥60 showed significantly increased interleukin-6, plasminogen-activator-inhibitor-1, tissue-plasminogen-activator, fibrinogen and increased ultrasensitive-C-reactive-protein compared to the low risk group (FLI≤20). Analysis of FFA indicated a less pronounced decrease of plasma FFA levels during the oral-glucose-tolerance-test in subjects with FLI≥60. History of GDM plus FLI≥60 conferred a high risk for the manifestation of diabetes over 10 years of observation as compared to pGDMs with FLI≤20 (HR:7.85, Cl:2.02–30.5, p = 0.003).

Conclusion

FL is closely linked to GDM, especially to IR and inflammation. Most interestingly, subjects with the highest FLI values showed significant alterations in FFA kinetics and a higher risk to develop T2DM in future.     

The Rationale for Prandial Glycemic Control in Diabetes Mellitus

Background:Diabetes mellitus (DM) is of epidemic proportions worldwide, and its microvascular and macrovascular complications have been well described. Achieving glycemic control has been demonstrated to reduce patients' risk of developing these complications.Objective:The objective of this article was to examine how prandial hyperglycemia-especially postprandial hyperglycemia (PPHG)-affects overall glycemic control and the complications of DM and to discuss the pharmacologic agents available to reduce PPHG.Methods:Materials used for this article were identified through a MEDLINE search of the literature (1975–2006). English-language randomized, controlled, prospective, cohort, and observational studies were chosen using the search terms postprandial hyperglycemia, oxidative stress, cardiovascular disease, macrovascular disease, microvascular disease, lipidemia, and coagulation.Results:Data show that controlling prandial hyperglycemia reduces the risk of cardiovascular disease (CVD) andmicrovascular complications, lowers glycosylated hemoglobin levels, causes less oxidative stress, and leads to a more favorable coagulation and postprandial lipidemia profile. Guidelines for targeting PPHG are becoming standard, and various pharmacologic agents (eg, a-glucosidase inhibitors, amylin analogues, incretin mimetics, rapid-acting insulins and insulin analogues, meglitinide analogues) that target PPHG may also improve overall glycemic control and reduce CVD risk.Conclusions:Although the level of hyperglycemia that leads to microvascular and macrovascular complications inpatients with DM remains to be elucidated, it appears prudent to address prandial hyperglycemia, especially PPHG, rather than focus solely on fasting glucose levels. Clinicians should consider incorporating agents that lower PPHG in their treatment of patients with DM.     

Influence of Glycemic Variables on Hemoglobin ALC

ObjectiveTo assess the influences of a wide variety of glucose variables on hemoglobin A1c (A1C).MethodsThe Diabetes Control and Complications Trial database, restricted to volunteers whose 7-point-daily capillary glucose profiles were complete in ≥ 80% of quarterly collections and who were in the study for ≥ 4 years, was used for analysis. Regression analyses were done to develop an equation for estimating A1C based on concurrent and prior mean blood glucose (MBG) values. The multivariate coefficient of determination (R²) was calculated for MBG, mean postprandial blood glucose, mean preprandial blood glucose, digestive glycemia, interdigestive glycemia, individual time points of the 7-point glucose profile, range of blood glucose, SD of blood glucose, M-value, and mean amplitude of glycemic excursions in relationship to A1C. By using regression analysis, the correlation between A1C and MBG within each study subject was determined.ResultsThe most accurate prediction of A1C was obtained from the concurrent MBG. With use of univariate analysis, all glucose variables correlated significantly with concurrent A1C, the strongest correlation occurring with MBG. In multivariate analysis, the primary predictor of A1C was MBG; all other glucose variables added nothing to the models. Within-subject correlations between MBG and A1C showed considerable variation.ConclusionA1C correlates best with MBG derived from 7-point-daily capillary glucose profiles. The influences of glucose measured at specific time points during the day or various measures of glucose variability on A1C are less than that of MBG. Within the limitations of the intermittent glucose determinations, wide variations in the relationship of MBG to A1C among and within patients with type 1 diabetes remain unexplained. (Endocr Pract. 2007;13:350-354)     

Glycemic Control Promotes Pancreatic Beta-Cell Regeneration in Streptozotocin-Induced Diabetic Mice

Background

Pancreatic beta-cells proliferate following administration of the beta-cell toxin streptozotocin. Defining the conditions that promote beta-cell proliferation could benefit patients with diabetes. We have investigated the effect of insulin treatment on pancreatic beta-cell regeneration in streptozotocin-induced diabetic mice, and, in addition, report on a new approach to quantify beta-cell regeneration in vivo.

Methodology/Principal Findings

Streptozotocin-induced diabetic were treated with either syngeneic islets transplanted under the kidney capsule or subcutaneous insulin implants. After either 60 or 120 days of insulin treatment, the islet transplant or insulin implant were removed and blood glucose levels monitored for 30 days. The results showed that both islet transplants and insulin implants restored normoglycemia in the 60 and 120 day treated animals. However, only the 120-day islet and insulin implant groups maintained euglycemia (<200 mg/dl) following discontinuation of insulin treatment. The beta-cell was significantly increased in all the 120 day insulin-treated groups (insulin implant, 0.69±0.23 mg; and islet transplant, 0.91±0.23 mg) compared non-diabetic control mice (1.54±0.25 mg). We also show that we can use bioluminescent imaging to monitor beta-cell regeneration in living MIP-luc transgenic mice.

Conclusions/Significance

The results show that insulin treatment can promote beta-cell regeneration. Moreover, the extent of restoration of beta-cell function and mass depend on the length of treatment period and overall level of glycemic control with better control being associated with improved recovery. Finally, real-time bioluminescent imaging can be used to monitor beta-cell recovery in living MIP-luc transgenic mice.