Effects of estrogen/medrogestone therapy on the apoprotein B-containing lipoproteins in postmenopausal women with type 2 diabetes mellitus under satisfactory and non-satisfactory glycemic control.

BACKGROUND: Information is lacking on the effects of hormone replacement therapy in women with diabetes, especially during moderate chronic hyperglycemia. OBJECTIVES: To study the effects of HRT on the lipid profile and the low density lipoprotein subclass distribution in women with type 2 diabetes under satisfactory and non-satisfactory glycemic control. METHODS: Fifty-four postmenopausal women after a 6 week run-in diet were randomized to receive either placebo (HbA1c < 8%, n = 13; HbA1c > 8%, n = 17) or HRT (HbA1c < 8%, n = 11; HbA1c > 8%, n = 13) for 12 weeks. HRT consisted of cyclical conjugated estrogens 0.625 mg/day plus medrogestone 5 mg/day. At the beginning and at the end of each treatment period the LDL subclass distribution was estimated by density gradient ultracentrifugation. RESULTS: At the baseline and during the study, the HbA1c level was significantly higher in hyperglycemic patients than in the near-normoglycemic controls (baseline 10.2 +/- 2.9 vs. 6.5 +/- 0.7%, P < 0.01). They showed a trend for higher total and LDL cholesterol, triglycerides and lower high density lipoprotein-cholesterol compared to near-normoglycemic controls, as well as significantly higher triglyceride concentrations in very low density lipoprotein, intermediate density lipoprotein and LDL-1 particles and cholesterol content in LDL-1 and -2 particles. HRT decreased LDL-cholesterol in both groups. In the normoglycemic patients a small increase in HbA1c was observed (6.5 +/- 0.7 vs. 7.4 +/- 1%, P = 0.04). In all cases, HRT did not modify the proportion of LDL represented by denser LDLs. CONCLUSIONS: HRT did not modify the LDL subclass distribution, even in the presence of moderate chronic hyperglycemia in women with type 2 diabetes.

Early-onset type 2 diabetes: metabolic and genetic characterization in the mexican population.

The objective of this study was to investigate possible defects in the insulin sensitivity and/or the acute insulin response in a group of Mexican patients displaying early-onset type 2 diabetes and to evaluate the contribution of mutations in three of the genes linked to maturity-onset diabetes of the young. We studied 40 Mexican patients with an age of diagnosis between 20 and 40 yr in which the insulin sensitivity as well as the insulin secretory response were measured using the minimal model approach. A partial screening for possible mutations in 3 of the 5 genes linked to maturity-onset diabetes of the young was carried out by PCR-single strand conformation polymorphism analysis. A low insulin secretory capacity (AIRg = 68.5 +/- 5 muU/mL.min) and a near-normal insulin sensitivity (3.43 +/- 0.2 min/muU.mL x 10(4)) were found in these patients. Among this group we found two individuals carrying missense mutations in exon 4 of the hepatocyte nuclear factor-1alpha (HNF-4alpha) gene (Asp(126)-->His/Tyr and Arg(154)-->Gln, respectively) and one carrying a nonsense mutation in exon 7 of the HNF-1alpha gene (Gln(486)-->stop codon); 7.5% had positive titers for glutamic acid decarboxylase antibodies. Thirty-five percent of cases had insulin resistance; these subjects had the lipid abnormalities seen in the metabolic syndrome. A defect in insulin secretion is the hallmark in Mexican diabetic patients diagnosed between 20 and 40 yr of age. Mutations in either the HNF-1alpha or the HNF-4alpha genes are present among the individuals who develop early-onset diabetes in our population. These particular sequence changes have not been previously reported and therefore represent putative new mutations. Even in the absence of endogenous hyperinsulinemia, insulin resistance is associated with an adverse lipid profile.

Comparing easy and accessible parameters of glycemic control in type 2 diabetes.

BACKGROUND: HbA1c is considered the gold standard of long-term glycemic control and is recommended as a routine test for every diabetic patient. However, its common use in clinical practice has some problems related to lack of standardization and its relative cost. Recent studies have suggested, that postprandial blood glucose could be better than a fasting sample, as a marker of diabetes control. The objective of the present study was to evaluate the relative value of plasma glucose samples at different times of the day, and easy and accessible programs for home blood and urinary glucose measurements compared with HbA1c in assessing the mean glycemic control of type 2 diabetic patients. METHODS: Sixty type 2 diabetic patients were instructed to do home blood and urine glucose monitoring for two months, at the end, plasma glucose profiles were obtained. RESULTS: The mean of all the capillary BG measurements had the best correlation with the HbA1c (r = 0.84, p < 0.001), followed by the mean of the capillary BG measurements before breakfast and supper (r = 0.82, p < 0.001), and the 2 hr. postbreakfast plasma glucose (r = 0.79 p < 0.001). The fasting PG had a low correlation (r = 0.65, p < 0.001), but a good sensitivity to predict a fair or a poor metabolic control. Diabetes duration and type of treatment explained 17% and 28% of variance in HbA1c levels. CONCLUSIONS: A bimonthly fasting PG correlated well with the glycosylated hemoglobin and is the easiest and cheapest way of monitoring glycemic control in type 2 diabetic patients with some preserved insulin reserve (diabetes for less than 10 years and on treatment with only one hypoglycemic agent). A sample of capillary BG, fasting, once per week correlates better with the HbA1c than a fasting PG every 2-3 months. The 2 hr and 5 hr postbreakfast PG have a good correlation with the HbA1c, but are not a substitute for doing BG monitoring. Glycosuria may be a useful parameter to rule out a fair or poor metabolic control in some patients.

Acarbose vs. bedtime NPH insulin in the treatment of secondary failures to sulphonylurea-metformin therapy in type 2 diabetes mellitus.

OBJECTIVE: To evaluate the efficacy of acarbose in the treatment of secondary failures to sulphonylurea-metformin therapy, its comparison against bedtime NPH insulin, and to measure the changes in postprandial metabolism resulting from both treatments. METHODS: One hundred type 2 diabetic patients in a secondary failure were included. The study begun with a run-in diet period of 6 weeks, in which an isocaloric diet was prescribed. Only subjects who continued hyperglycaemic were randomly assigned to placebo and acarbose (n = 17) or bedtime NPH insulin (n = 12). Acarbose (300 mg/day) or placebo were administered using a randomized, double blind, crossover design. Treatment periods of 3 months were separated by a 3-week washout period. Insulin was administered during 3 months. At the beginning and the end of each treatment period, an i.v. glucose tolerance test and a meal test were performed. Safety tests were done every 4 weeks. RESULTS: Acarbose resulted in a small but significant improvement in fasting plasma glucose (13.5 +/- 2.4 vs. 11.3 +/- 3.9 mmol/l, p = 0.05), HbA1c (11.1 +/- 3.4 vs. 10.3 +/- 2.5%, P = 0.3) and in a decreased plasma glucose during the meal test. Bedtime insulin significantly decreased fasting plasma glucose (13.1 +/- 2.9 vs. 8.2 +/- 2.3 mmol/l, p < 0.01), HbA1c (11.7 +/- 2.9 vs. 9.4 +/- 2.7%, p < 0.01) and plasma cholesterol. No change in insulin secretion resulted from insulin and acarbose treatment. CONCLUSIONS: Acarbose decreases blood glucose in secondary failure to sulphonylurea-metformin therapy; however, the decrease is not enough to reach the desired metabolic control. Bedtime NPH insulin is, by far, a more effective alternative.