Claude K Lardinois

Effect of Acarbose on Carbohydrate and Lipid Metabolism in NIDDM Patients Poorly Controlled by Sulfonylureas

The ability of acarbose to lower plasma glucose concentration was studied in 12 patients with noninsulin-dependent diabetes mellitus (NIDDM) who were poorly controlled by diet plus sulfonylurea drugs. Patients were studied before and 3 mo after the addition of acarbose to their treatment program, and a significant improvement in glycemic control was noted. Although the decrease in fasting plasma glucose concentration was modest (12.0 ± 0.8 to 10.8 ± 0.3 mM), average postprandial plasma glucose concentration decreased by 3.4 mM. When acarbose therapy was discontinued in 5 patients, plasma glucose levels rapidly returned toward pretreatment levels. In addition to the improvement in glycemia, acarbose treatment also led to a significant reduction in HbA1c (7.4 ± 0.2 to 6.4 ± 0.2%, P < 0.01) and triglyceride (2.4 ± 0.1 to 2.1 ± 0.1 mM, P < 0.01) concentrations. Neither the plasma insulin response to meals nor insulin-stimulated glucose uptake improved with acarbose therapy, consistent with the view that acarbose improves glycemic control by delaying glucose absorption. Considerable individual variation was noted in the response to acarbose, and the results in 4 patients were dramatic, with striking reductions in both fasting and postprandial glucose concentrations. The addition of acarbose to patients with NIDDM not well controlled by sulfonylureas appears to have significant clinical benefit.

Insulin secretion and action in noninsulin-dependent diabetes mellitus: Is insulin resistance secondary to hypoinsulinemia?

The insulin-stimulated glucose metabolic clearance rate, assessed by the insulin clamp technique, was compared in 40 normal subjects and 40 age- and weight-matched patients with noninsulin-dependent diabetes mellitus. These studies were conducted at steady-state plasma insulin levels of approximately 100 microU/ml, and the mean (+/- standard error of the mean) glucose metabolic clearance rate of patients with noninsulin-dependent diabetes mellitus was 81 +/- 9 ml/m2 per minute, as compared with a value of 235 +/- 14 ml/m2 per minute for normal subjects. This difference was highly statistically significant (p less than 0.001) and documents the extreme resistance to insulin-stimulated glucose utilization seen in noninsulin-dependent diabetes mellitus. Patients with noninsulin-dependent diabetes mellitus were also shown to have a lower than normal plasma insulin response to an oral glucose challenge. In contrast, ambient plasma insulin concentrations of normal subjects and patients with noninsulin-dependent diabetes mellitus were found to be quite comparable when measured throughout the day in response to the ingestion of conventional mixed meals. Consequently, absolute hypoinsulinemia is not characteristic of patients with noninsulin-dependent diabetes mellitus under conditions of daily living. Finally, the ability of intensive insulin treatment to improve insulin resistance was studied after one and six weeks of therapy. These results indicated that successful control of hyperglycemia led to a significant improvement in insulin action as early as one week after the initiation of insulin therapy, with no further changes noted after prolonged insulin administration. The degree to which insulin action approached normal values was greater when studies were carried out at circulating insulin levels of approximately 2,000 microU/ml as compared with insulin levels of approximately 100 microU/ml, but in both instances insulin-treated diabetic patients remained insulin-resistant as compared with normal subjects. These results have corroborated the fact that abnormalities of both insulin action and secretion can be documented in patients with noninsulin-dependent diabetes mellitus. However, patients with noninsulin-dependent diabetes mellitus were not found to be absolutely hypoinsulinemic in their daily existence, and control of their hyperglycemia with exogenous insulin did not restore insulin-stimulated glucose utilization to normal. Consequently, these data are not consistent with the view that the insulin resistance in noninsulin-dependent diabetes mellitus is entirely a secondary consequence of the hypoinsulinemia presumed to be present in these patients.

Insulin-stimulated Glucose Disposal Increases with Time in Patients with Non-insulin-dependent Diabetes Mellitus

The relative effects of time versus ambient glucose concentration on insulin-stimulated glucose uptake was estimated by performing 5-h insulin clamp studies in patients with NIDDM. Each experimental subject was studied three times, at steady-state plasma insulin levels ∼2000 μU/ml, but at different steady-state, plasma glucose concentrations (studies A, B, and C). Study A consisted of a 5-h clamp, with plasma glucose level maintained at the basal level of fasting hyperglycemia; study B differed in that the basal level of fasting hyperglycemia was reduced during the first hour to ∼80 mg/dl, and maintained there for the next 4 h; and study B was carried out by clamping the patient at the basal glucose level for 2 h, lowering the glucose concentration to approximately 80 mg/dl during the third hour, and then clamping at this level for the last 2 h. The glucose metabolic clearance rate (MCR) was calculated from 60 to 120 min and from 240 to 300 min during each study, and the results indicated that values for glucose MCR were time dependent, being significantly greater (20–60%) in the fifth than in the second hour in two (studies A and B) of the three studies. In contrast, glucose MCR was independent of plasma glucose concentration, and relatively constant in each subject, as long as it was measured during the same time period. The time-dependent increase in glucose MCR was associated with an approximate 30% increase in steady-state plasma insulin concentrations when comparing the second and fifth hours. These data emphasize the time-dependent increase in insulin-stimulated glucose disposal that occurs in insulin clamp studies, and point out the potential difficulties in interpretation that can evolve from sequential estimates of insulin-stimulated glucose disposal. In addition, they provide additional evidence that measurement of glucose MCR can be used to compare insulin stimulated glucose disposal in patients with NIDDM under the conditions used in these studies.

Dissimilar Fatty Acid Composition of Standard Rat Chow

The lower incidence of coronary heart disease in populations consuming polyunsaturated fatty acids has spurred interest in the possible cardioprotective nature of these fatty acids. Furthermore, the source of dietary fats may modify the natural history of some chronic inflammatory disorders such as rheumatoid arthritis and systemic lupus erythematosus. Some studies examining these issues have involved animals fed a standard chow diet to which the desired fatty acids were added. Our observation that two lots of standard rat chow varied considerably in fatty acid composition, prompted us to analyze two additional standard rat chow lots for fatty acid composition. Each lot was extracted and fatty acid chain length determined by gas chromatography with the percentage of total fatty acids determined by integration. A wide variation in the total saturated (27.4-42.1%), monounsaturated (8.3-30.9%), omega 6 (17.2-44.2%), and omega 3 (3.8-11.2%) fatty acids was observed. By one-way analysis of variance, significant differences (p less than 0.025) between the various lots were observed for total saturated, monounsaturated, and omega 6 fatty acid groups. These findings suggest that fatty acid composition of standard rat chow is not similar. If the baseline fatty acid composition is critical to the experimental design, custom chow diets should be used.

Hyperfiltration and Albuminuria—A Deadly Combination

I ndividuals with chronic kidney disease (CKD) are at high risk of coronary heart disease (CHD), and roughly half die of CHD without developing end-stage renal disease. Two key kidney measurements: estimated glomerular filtration rate (eGFR) and albuminuria, are consistently associated with high CHD risk. An eGFR greater than 105 ml/min per 1.73m2 (hyperfiltration) and an albumin-to-creatinine ratio (ACR) greater than 5 mg/g are both independently associated with an increased risk of CHD. Therefore, eGFR and ACR should be taken into account for cardiovascular prediction.

Nutritional Recommendations—We Must Get Them Right at Last

Almost four decades ago, the American medical establishment was bamboozled into believing that consumption of dietary fat and cholesterol were critical factors in cardiovascular disease. Many trace the confusion to Ancel Keys, who strongly believed that dietary fat and cholesterol were closely related to the development of heart disease. In 1970, Keys published the Seven Countries Study (which included Italy, Greece, Yugoslavia, Finland, the Netherlands, Japan, and the US), which showed that dietary saturated fat intake increased total cholesterol, and this was associated with an increase coronary mortality. However, data were actually available for 22, rather than seven, countries and, in the analysis of all the data, a poor relationship between total fat intake and heart disease can be seen. So why did Keys omit countries where the consumption of total and saturated fat were higher, yet the risk of heart disease was low? Many critics conclude that the study was biased in favor of his hypothesis.

No More Heart Disease— Addressing Major Modifiable Risk Factors in Type 2 Diabetes

Cardiovascular disease (CVD) is the leading cause of death among people with type 2 diabetes, yet much of the population remains unaware of the risk. People with diabetes are two to four times more likely to develop CVD due to a variety of risk factors. Large studies have shown that 85–90 % of patients with CVD have one or more of the traditional modifiable risk factors. Important modifiable risk factors include obesity, physical exercise, nutritional factors, alcohol consumption, tobacco smoking, vitamin D, psychosocial factors, dyslipidemia, hypertension, albuminuria, and dysglycemia. This article will review the impact that each of these modifiable factors has on CVD risk. The importance of aspirin therapy will also be addressed in light of the results of a number of studies that failed to demonstrate a convincing cardioprotective benefit of low-dose aspirin in patients with type 2 diabetes. Gene polymorphisms are also emerging as important contributors to CVD development, but will not be addressed in this article.

Medical Nutrition Therapy - The Relationship of Dietary Fat and Carbohydrate Metabolism in Patients with Type 2 Diabetes

The optimal composition of macronutrient intake for people with type 2 diabetes has been a subject of much debate. There are differing lines of thought as to the appropriate amount of carbohydrate, protein and fat that should be consumed to best regulate glucose control. This article will review literature on macronutrient intake in relation to glucose control in patients with type 2 diabetes, with a special emphasis on the impact of dietary fat. Monounsaturated Fat The American Dietetic Association recommends that 60‐70% of total calories be derived from monounsaturated fat (MUFA) and carbohydrate for persons with type 2 diabetes.1 However, the specific amount and type of carbohydrate and fat in the diet has been the subject of numerous studies. A comprehensive meta-analysis in people with diabetes concluded that, compared with high-carbohydrate diets, high-MUFA diets improve glycaemic profiles and have a favourable impact on lipoprotein metabolism.2 Whether this is due to a direct impact on insulin secretion or from a reduction in the carbohydrate load has also been debated. One study3 found that diets with a high content of MUFA-rich foods provide a degree of metabolic control that is similar to or perhaps better than that obtained with a high-carbohydrate diet. The author postulates that a healthy diet does not necessarily have to be a low-fat one because a variety of MUFA-rich foods can be incorporated into the diet to increase palatability and therefore lead to better compliance.