The efficacy and safety of miglitol therapy compared with glibenclamide in patients with NIDDM inadequately controlled by diet alone.

OBJECTIVE: To compare the therapeutic effects of the alpha-glucosidase inhibitor miglitol (BAY m 1099), the sulfonylurea glibenclamide, and placebo on parameters of metabolic control and safety in patients with NIDDM that is inadequately controlled by diet alone. RESEARCH DESIGN AND METHODS: After a 4-week placebo run-in period, 201 patients in 18 centers in 4 countries were randomized in a double-blind manner to miglitol (50 mg t.i.d., followed by 100 mg t.i.d.), glibenclamide (3.5 mg q.d/b.i.d.), or placebo for 24 weeks. Efficacy criteria were changes from baseline of HbA1c, fasting and postprandial blood glucose and insulin levels, body weight, and serum triglycerides. RESULTS: Efficacy was assessed in 119 patients who completed the full protocol, and the results were similar to those obtained in 186 patients who fulfilled the validity criteria for analysis. Compared with placebo, mean baseline-adjusted HbA1c decreased by 0.75% (P = 0.0021) and 1.01% (P = 0.0001) in the miglitol and glibenclamide treatment groups, respectively. Blood glucose decreased slightly in the fasting state and considerably in the postprandial state in both treatment groups but not in the placebo group. Fasting insulin levels increased slightly (NS) in all treatment groups; however, postprandial insulin levels decreased with miglitol, while increasing markedly with glibenclamide (P = 0.0001 between all treatment groups). Gastrointestinal side effects (flatulence and diarrhea) occurred mostly in the miglitol-treated patients, while some glibenclamide-treated patients had symptoms suggestive of hypoglycemia. CONCLUSIONS: Miglitol monotherapy is effective and safe in NIDDM patients. Compared with glibenclamide, it reduced HbA1c less effectively and caused more gastrointestinal side effects. On the other hand, glibenclamide, unlike miglitol, tended to cause hypoglycemia, hyperinsulinemia, and weight gain, which are not desirable in patients with NIDDM.

[Incidence of severe hypoglycemia in relation to metabolic control and patient knowledge]. / Inzidenz schwerer Hypoglykämien in Abhängigkeit von der Stoffwechselqualität und dem Patientenwissen.

BACKGROUND: The question whether the incidence of severe episodes of hypoglycaemia in type I and type II diabetics correlates with the level of the patient's knowledge about hypoglycaemia and the quality of metabolic control. PATIENTS AND METHODS: A total of 234 consecutive type I diabetics (age and diabetes duration 48 and 16 years, respectively; blood glucose, self-monitored 63%) and 237 type II diabetics treated with glibenclamide (mean dose 6.7 mg/day) (age and diabetes duration 65 and 9 years, respectively; glucosuria, self-monitored 36%) who attended the Berlin outpatient diabetic centre were investigated. RESULTS: Of the type I diabetics 23 (9.8%) experienced a total of 32 severe episodes of hypoglycaemia (incidence 0.14 per patient/year). Patients at risk of experiencing hypoglycaemia were about 20 years younger, injected insulin more often (3.8 vs 2.3 injections/day; p < 0.01) and had a lower HbA1 level (7.8% vs 9.0%; p < 0.01) than those having no hypoglycaemic reactions. Ten of the 23 diabetics suffering severe episodes of hypoglycaemia showed signs of kidney disease. The most common causes of hypoglycaemia were dietary errors (18.7%) or incorrect doses of insulin (12.5%), alcohol consumption (12.5%) and unusual physical exertion (23%). In terms of their knowledge about hypoglycaemia, there were no notably differences between patients with and those without hypoglycaemic reactions. Among the 237 type II diabetics treated with glibenclamide, three (1.3%) experienced one episode of severe hypoglycaemia each (incidence: 0.013 patient/year). Old age, maximum dosage of glibenclamide (15 mg/day) and multimorbidity were characteristic of these patients. Enquiries showed that only 49% (n = 160) of all type II diabetes had adequate knowledge about hypoglycaemia. CONCLUSION: In type I diabetics, there appears to be no relationship between the hypoglycaemia risk and the patient's theoretical knowledge of hypoglycaemia. In future, apart from theoretical knowledge, more attention must be paid to practical training to improve awareness of hypoglycaemia. Educational programs for type II diabetics must attach more weight to the problem of hypoglycaemia.

[The "diabetic foot" syndrome. Association with other complications and the incidence of amputation]. / Das Syndrom des "diabetischen Fusses". Vergesellschaftung mit anderen Komplikationen sowie Inzidenz von Amputationen.

BACKGROUND: Only few studies have investigated the incidence of foot lesions and amputation rate in diabetic patients. PATIENTS AND METHOD: Thus, the 10-year incidence rates of first lower extremity amputation were studied in 560 diabetic patients, aged 35 to 55 years at baseline and followed up within the WHO-Multinational Study of Vascular Disease in Diabetes. Furthermore, we studied the frequency of other complications in 51 outpatients with "the diabetic foot syndrome". RESULT: In type 1 diabetic patients, the incidence rates (7.2/1,000 person-years for men and 7.6/1,000 person-years for women) were higher as compared with type 2 diabetic patients (4.1/1,000 and 4.3/1,000 per person-years for men and women, respectively). In multivariate analysis, duration of diabetes, hypertension, claudicatio intermittens, retinopathy and proteinuria emerged as potential risk factors. Outpatients with the "diabetic foot syndrome" were characterized by an advanced age and a long duration of diabetes (59 years and 22.5 years, respectively). 30 patients (58%) had type 1 diabetes and 21 (42%) had type 2, diabetes mellitus. The proportion of complications was as follows: foot lesions due to diabetic neuropathy or peripheral ischaemic vessel disease in 45.1% and 25.5%, and a combination of both in 29.4%. The majority of type 2 diabetic patients had lesions due to peripheral ischaemic vessel disease (77%); these patients were 10-years older as compared with patients with neuropathic lesions. Proliferative retinopathy was 4 times as high in patients with neuropathic lesions as compared with patients with ischaemic lesions (61% vs 15%). CONCLUSION: The findings once again emphasize the importance of education and training programs in elderly diabetic patients.

[The effect of blood pressure-reducing therapy with captopril on tubular marker excretion in type-1 diabetics with nephropathy]. / Einfluss einer blutdrucksenkenden Therapie mit Captopril auf die Exkretion tubulärer Marker bei Typ-I-Diabetikern mit Nephropathie.

A prospective open clinical trial was carried out with 23 hypertensive type I diabetics (13 men, ten women, mean age 49 +/- 9.1 years, duration of diabetes 18 +/- 9.1 years) with early nephropathy. Glomerular and tubular renal function and metabolic parameters were monitored during 8 months' treatment with the angiotensin converting enzyme (ACE) inhibitor, captopril, in addition to previous antihypertensive treatment with one or more drugs. Blood pressure control tended to improve on captopril (systolic pressures 152 +/- 13 vs 140 +/- 13 mm Hg, P < 0.05; diastolic pressures 89 +/- 10 vs 87 +/- 10 mm Hg, not significant). Proteinuria (> 0.5 g/24 hours) fell into the microalbuminuria range (albumin excretion 2-20 mg/mmol creatinine) in four out of 13 patients, and microalbuminuria disappeared in four out of ten patients. Urinary levels of the brush border enzyme N-acetyl-beta-D-glucosaminidase (NAG), a marker of tubular dysfunction, were initially raised and fell significantly after 8 months' treatment with captopril (20.3 +/- 14.4 vs 8.8 +/- 8.1 U/g creatinine; P < 0.01). Captopril did not affect metabolic control (HbA1, total, HDL and LDL cholesterol, triglycerides, apolipoproteins A1 and B) or the insulin dosage. These results show that long-term treatment with captopril may favourably influence both albumin excretion and NAG activity, a marker of tubular dysfunction, in type I diabetics with nephropathy.

[Screening studies in diagnosis of diabetes. Do they still have practical value?]. / Screening-Untersuchungen in der Diabetesdiagnostik. Haben sie noch eine praktische Bedeutung?

The WHO has defined standardized diagnostic criteria for manifest diabetes mellitus and disorders of glucose tolerance. Owing to a low level of sensitivity and only moderate specificity, coupled with an unfavorable cost-benefit rating, glucosuria screening is not suitable for large-scale use at population level and, as recommended by the WHO, should be replaced by plasma glucose screening. The method of choice for the latter is the determination of the fasting plasma glucose level. Its use should be restricted to target groups with a high risk of contracting diabetes. In the doctor's office, a health check is of particular importance for the diagnosis of type 2 diabetes, which is usually asymptomatic. Screening for diabetes with the aid of a 50 g oral dose of glucose to detect gestational diabetes is a must during pregnancy.

[Effect of fish oil concentrate on the lipoprotein profile of patients with type II diabetes mellitus]. / Zur Wirkung von Fischölkonzentrat auf das Lipoproteinprofil bei Patienten mit Diabetes mellitus Typ II.

Non-insulin-dependent diabetes mellitus (NIDDM) is associated with increased very-low-density lipoprotein (VLDL) and triglyceride concentrations as abnormalities of low-density lipoprotein (LDL) composition. Because fish oil has a strong triglyceride lowering effect in case of normolipemic subjects, we investigated the influence of supplementary fish oil diet in patients suffering from NIDDM (n = 19), who until now were not treated by drugs but only by diet. The study was started with a placebo-run-in-period for four weeks (phase I, 6 g rape seed oil capsules/d), followed by a verum period for twelve weeks (phase II, 6 g fish oil concentrate capsules/d), and a wash-out-period for four weeks (phase III, 6 g rape seed oil capsules/d). The fish oil supplementation contained at least 3 g eicosapentenoic and docosahexenoic acid. The lipoproteins, apolipoproteins, blood glucose, and insulin level (fasting and after load test) were checked at the beginning and at the end of each phase. In comparison to the placebo rape seed oil supplementation, the fish oil diet effected a decrease of serum triglycerides by 29%. LDL-cholesterol increased by 9%, HDL-cholesterol by 9% (especially HDL2-cholesterol), and apolipoprotein B by 4%. Apolipoprotein A-I was reduced by 9%. The fasting blood glucose and the glucose load test as the insulin level (fasting and after load test) showed no significant changes at the end of the verum period in comparison to the run-in-phase.(ABSTRACT TRUNCATED AT 250 WORDS)

[Trends in prescribing oral antidiabetic drugs. An analysis of the Berlin diabetes register covering 28 years]. / Trends in der Verordnung von oralen Antidiabetika. Eine Analyse des Berliner Diabetesregisters über 28 Jahre.

On the basis of the data collected by the (East) Berlin diabetes register, the prevalence of diabetes and trends in the prescription of oral antidiabetic agents over almost three decades were analysed. Between 1961 and 1989, the diabetic registration rate increased threefold, from 13,700 to 49,000. This corresponds to an increase in prevalence from 1.3% to 3.8%. At the beginning of the nineteen-sixties, only carbutamide and tolbutamide were prescribed, the respective percentages being 29% and 71%. From 1969 onward, the percentage of carbutamide decreased drastically and was no longer prescribed after 1973. With the introduction of the sulfonylureas ureas of second generation in 1969, the prescription of tolbutamide and glibenclamide showed an inverse evolution. In 1989, the prescription rate of tolbutamide was only 10% of all oral antidiabetics, while 88% of the patient group received glibenclamide. Since 1965, biguanides have been increasingly prescribed, reaching a peak of 32% of all prescriptions of oral diabetics by 1975. Thereafter, prescription of biguanides decreased. In 1979, biguanides accounted for only about 5% of all oral antidiabetics prescribed, and in 1989, for only 0.3%. The introduction of structured dietary teaching programs for type 2 diabetics resulted in a drastic change in the prescription of oral diabetics in the case of newly diagnosed patients: in 1968, primary management with oral antidiabetics peaked, accounting for 43.2% of the cases (newly diagnosed diabetics 3.049). This percentage decreased progressively and, in 1985, reached a figure of 17.5% in new cases of diabetes (total number of newly diagnosed cases 3.936). Since 1975, the percent of cases managed primarily with insulin has remained constant.(ABSTRACT TRUNCATED AT 250 WORDS)

Improvement of metabolic control and changes of fatty acid composition do not alter platelet aggregability and thromboxane production in type 2 diabetes mellitus.

To evaluate whether improvement of metabolic control or changes in fatty acid composition of serum lipids may alter thromboxane (TXB2) formation and platelet function we followed up 25 newly diagnosed type 2 diabetics without angiopathy for about 6 months. Improvement of metabolic control was associated with significant decrease in total cholesterol (C), HDL-C, LDL-C, triglycerides (TG) and ratios of total C/HDL-C and LDL-C/HDL-C, respectively. Palmitic acid of TG and phospholipids decreased significantly whereas linoleic acid increased in the two serum lipids. The ADP-induced platelet aggregability and sensitivity were not altered. There was even no effect on TXB2 synthesis capacity of clotting whole blood during 6 months of treatment. Platelet aggregability and TXB2 formation were not correlated to the degree of metabolic control, nor was there any correlation to serum lipids and their fatty acid composition.

Thromboxane production and platelet aggregation in type 2 diabetes mellitus without vascular complications.

Diabetic individuals frequently have platelet hyperaggregability and increased thromboxane (TXB2) production. To evaluate whether improvement of metabolic control or changes in fatty acid composition of serum lipids might alter thromboxane (TXB2) formation and platelet function, we followed up 25 newly diagnosed type 2 diabetics without angiopathy for about 6 months. Improvement of metabolic control (HbA1, fell from 12.0 +/- 0.3 to 9.0 +/- 0.3%; p less than 0.01) was associated with significant decrease in total cholesterol, triglycerides, and ratios of total cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol. Palmitic acid of phospholipids decreased significantly, whereas eicosapentaenoic acid increased. Regardless of this, the ADP-induced platelet aggregability and sensitivity were not altered. There was no effect whatever on the TXB2 synthesis capacity of clotting whole blood (204.9 +/- 25.0 vs 222.8 +/- 32.0 ng/ml) over 6 months of treatment. Platelet aggregability and TXB2 formation were not correlated to the degree of metabolic control, nor were there any correlations to serum lipids and their fatty acid composition. Thus, we are tempted to speculate that glucose metabolism in diabetes itself does not affect platelet aggregation or TXB2 formation in type 2 diabetes mellitus.