Ten-year follow-up of subjects with impaired glucose tolerance: prevention of diabetes by tolbutamide and diet regulation.

In a diabetes detection survey carried out between 1962 and 1965, 2477 (1.1%) of 228,883 subjects had Clinistix-positive glucosuria after a carbohydrate-rich luncheon meal. Of these 2477, 578 displayed impaired tolerance to oral glucose without having manifest diabetes. From this group, 267 men were divided into five groups and subjected to the following treatments and controls: (a) diet regulation and 0.5 g tolbutamide t.i.d. (N = 49), annual oral glucose tolerance test (OGTT); (b) diet regulation and one placebo tablet t.i.d. (N = 48), annual OGTT; (c) diet regulation only (N = 50), annual OGTT; (d) no treatment (N = 61), annual OGTT; and (e) no treatment, OGTT at follow-up (N = 59 at follow-up). In addition, a control group was included comprised of men with normal OGTT (N = 52). At follow-up, 29% of those without diet regulation and medication (group e: N = 59) had developed diabetes. Of those on diet regulation, but without active medication (group b plus group c, N = 98), 13% had diabetes. No individual maintaining tolbutamide and diet regulation (N = 23) had progressed to diabetes. In this group, 80% of those later examined (N = 11) had serum tolbutamide concentrations in the therapeutic range. No individual with initially normal OGTT developed diabetes or impaired OGTT. The findings suggest that normal oral glucose tolerance signifies little risk of progress to impaired glucose tolerance and manifest diabetes, whereas impaired glucose tolerance is associated with a high risk of progression to diabetes. In addition, it seems possible that treatment with diet regulation, in combination with tolbutamide, may prevent or postpone progression from impaired glucose tolerance to manifest diabetes.

Preventing non-insulin-dependent diabetes.

Many risk factors for non-insulin-dependent diabetes mellitus (NIDDM), such as obesity, physical inactivity, and high-fat diet, can potentially be modified. Furthermore, some of the metabolic abnormalities, such as insulin resistance and impaired glucose tolerance, that predict diabetes can be improved by behavior modification and drug treatment. Thus, at least to some extent, NIDDM may be preventable. Several small clinical trials have addressed the hypothesis that NIDDM can be prevented by dietary modification, physical activity, or drug treatment. Some studies suggest a preventive effect, but the conclusions are limited by considerations of sample size, randomization, or intensity of the interventions. Consequently, the hypothesis that NIDDM is preventable requires further testing.

Improvement of the plasma lipoprotein pattern after institution of insulin treatment in diabetes mellitus.

Plasma lipids and lipoproteins were studied in 26 nonobese diabetic patients, either newly diagnosed or unsatisfactorily controlled by oral antidiabetic treatment. Measurements were performed before and 3-4 mo after the institution of insulin treatment. In a subgroup of seven patients, the activities of lipoprotein lipase (LPL) and hepatic lipase (HL) in postheparin plasma and the elimination rate of exogenous triglyceride were also monitored. After beginning insulin treatment, diabetic control was improved as demonstrated by decreasing levels of HbA1. Mean plasma cholesterol and triglyceride levels decreased by about 10% (P less than 0.01) and 40% (P less than 0.05), respectively. The decrease in plasma cholesterol was largely accounted for by a fall in LDL cholesterol levels (-8%, P less than 0.05), while plasma HDL cholesterol concentrations increased by about 12% (P less than 0.01). The elimination rate of exogenous triglycerides increased significantly. There was a suggestive, but not significant, increase in LPL activity while the HL activity remained unchanged. It is concluded that the improved diabetic control after institution of insulin treatment results in a significant improvement of the plasma lipoprotein profile. Since the improvement of the lipoprotein pattern is not strictly correlated to the amelioration of indices reflecting glucose transport, we suggest that the plasma lipoprotein pattern may provide an additional tool for monitoring the degree of control in diabetes mellitus.

Therapeutic comparison of metformin and sulfonylurea, alone and in various combinations. A double-blind controlled study.

OBJECTIVE: To assess and compare the therapeutic efficacy and safety of metformin (M) and sulfonylurea (glyburide, G), alone and in various combinations, in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Of 165 patients (fasting blood glucose [FBG] > or = 6.7 mmol/l) initially treated with diet alone, 144 (FBG still > or = 6.7 mmol/l) were randomized to double-blind, double-dummy controlled treatment with M, G, or primary combination therapy (MG). The dose was titrated, with FBG < 6.7 mmol/l as target, using, at most, six dose levels. The first three dose levels comprised increasing single-drug therapy (M or G) or primary combination at increasing but low dosage (MGL), and the second three levels were composed of various high-dose combinations, i.e., add-on therapy (M/G or G/M) and primary combination escalated to high dosage (MGH). Medication was maintained for 6 months after completed dose titration. RESULTS: The FBG target was achieved in 9% of patients after diet alone. Single-drug therapy was insufficient in 36% and MGL in 25% (NS) of the randomized patients. There was further improvement in glucose control by the high-dose combinations. Mean FBG +/- SE was reduced (P = 0.001) from 9.1 +/- 0.4 to 7.0 +/- 0.2 mmol/l in those maintained on single-drug treatment or low-dose primary combination. Those treated with different high-dose combinations had a large mean FBG reduction, from 13.3 +/- 0.8 to 7.8 +/- 0.6 mmol/l. HbA1c levels showed corresponding reductions, and glycemic levels rose after drug discontinuation. Fasting C-peptide rose during treatment with G and MGL but not with M, while fasting insulin was not significantly changed. Meal-stimulated C-peptide and insulin levels were unchanged by M but increased by G and, to a lesser extent, by MGL. There were no significant insulin or C-peptide differences between the different high-dose combinations (M/G, G/M, and MGH). Body weight did not change following treatment with M or combination but increased by 2.8 +/- 0.7 kg following G alone. Blood pressure was unchanged. Overall effects on plasma lipids were small, with no significant differences between groups. Drug safety was satisfactory, even if the reporting of (usually modest) adverse events was high; the profile, but not the frequency, differed between groups. CONCLUSIONS: Dose-effect titrated treatment with either metformin or glyburide promotes equal degrees of glycemic control. The former, but not the latter, is able to achieve this control without increasing body weight or hyperinsulinemia. Near-normal glycemia can be obtained by a combination of metformin and sulfonylurea, even in advanced NIDDM.

Will sulfonylurea treatment of impaired glucose tolerance delay development and complications of NIDDM?

The chronic hyperglycemia of non-insulin-dependent diabetes mellitus (NIDDM) evolves gradually and is usually preceded by more transient hyperglycemia, classified as impaired glucose tolerance (IGT). Already in this phase, there is an increased risk of cardiovascular complications, and many IGT subjects, like NIDDM patients, often display several of the metabolic and circulatory disturbances that are associated with hyperglycemia, e.g., insulin resistance, hyperinsulinemia and/or hyperproinsulinemia, delayed insulin release, dyslipidemia, and hypertension. Therefore, and because untreated hyperglycemia is a self-perpetuating condition, early detection and early intervention may be necessary to prevent the progression and complications of NIDDM. This in turn would necessitate screening procedures, and the therapeutic goal should include both euglycemia and normalization of plasma insulin, plasma lipids, and blood pressure. A study in the German Democratic Republic indicated that the mortality in screening-detected NIDDM patients did not differ from that in patients detected in routine care. In a Swedish study on screening-detected NIDDM subjects, only those who had IGT rather than manifest NIDDM could maintain fasting blood glucose less than or equal to 6 mM for 5 yr by hypocaloric dietary regulation alone. In those with screening-detected NIDDM, the delayed acute insulin release and net postprandial hyperglycemia were improved by addition of glipizide, and most managed to attain and maintain fasting blood glucose less than or equal to 6 mM for approximately 2 yr after such addition. However, after 4 yr, there was an increase in blood glucose, suggesting that preventive intervention either may not be possible or may have to start in the IGT phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Family characteristics and life events before the onset of autoimmune type 1 diabetes in young adults: a nationwide study.

OBJECTIVE: To elucidate whether family characteristics and stressful life events were associated with onset of autoimmune type 1 diabetes in young adults. RESEARCH DESIGN AND METHODS: This investigation was based on a nationwide study (Diabetes Incidence Study in Sweden) of newly diagnosed patients aged 15-34 years. Patients clinically classified as type 1 diabetic with antibodies to islet cells and/or to GAD65 were compared with age- and sex-matched control subjects via questionnaire. The questionnaire covered diabetes heredity, social environment, educational level, and life events experienced during the 12 months before diagnosis. RESULTS: The rate of response was 82% for the diabetic patients and 65% for the control subjects. Questionnaires from 349 diabetic patients and 979 control subjects were considered. Diabetes in relatives was more frequent in the patients (odds ratio [OR]2.6) who were born in Sweden and whose mothers were of Swedish origin. No major stress factors were detected in the diabetic patients; however, in comparison with the control subjects, the diabetic patients had experienced fewer conflicts with their parents and had less often broken contacts with friends. CONCLUSIONS: Young adults with recent-onset type 1 diabetes were more exposed to heredity for diabetes, but no major prediabetic stress factors were detected. Our study does not directly support the concept that psychosocial stressful life events are involved in the development of autoimmune type 1 diabetes in young adults.

Islet cell and glutamic acid decarboxylase antibodies present at diagnosis of diabetes predict the need for insulin treatment. A cohort study in young adults whose disease was initially labeled as type 2 or unclassifiable diabetes.

OBJECTIVE: To clarify the predictive value of islet cell antibody (ICA) and GAD65 antibody (GADA) present at diagnosis with respect to the need for insulin treatment 6 years after diagnosis in young adults initially considered to have type 2 or unclassifiable diabetes. RESEARCH DESIGN AND METHODS: The patient material was representative of the entire Swedish population, consisting of patients who were 15-34 years old at diagnosis of diabetes in 1987-1988 but were not considered to have type 1 diabetes at onset. At follow-up, 6 years after the diagnosis, it was noted whether the patient was treated with insulin. The presence of ICA was determined by an immunofluorescence assay, and GADAs were measured by a radioligand assay. RESULTS: Six years after diagnosis, 70 of 97 patients were treated with insulin, and 27 of 97 patients were treated with oral drugs or diet alone. At diagnosis, ICAs and GADAs were present in 41 (59%) of 70 patients and 41 (60%) of 68 patients, respectively, of those now treated with insulin, compared with only 1 (4%) of 26 patients and 2 (7%) of 27 patients who were still not treated with insulin. For either ICA or GADA, the corresponding frequencies were 50 (74%) of 68 for patients who were later treated with insulin and 3 (12%) of 26 for those who were still not treated with insulin, respectively. The sensitivity for later insulin treatment was highest (74%) for the presence of ICA or GADA, and the specificity was highest (100%) for ICA and GADA. The positive predictive value was 100% for the combination of ICA and GADA, 98% for ICA alone, and approximately 95% for GADA alone. CONCLUSIONS: Determination of the presence of ICA and GADA at diagnosis of diabetes improves the classification of diabetes and predicts the future need of insulin in young adults.

Clinical and biochemical effects of spironolactone administered once daily in primary hypertension. Multicenter Sweden study.

In a prospective, double-blind, intraindividual, cross-over, placebo-controlled multicenter study, clinical and biochemical effects of once daily postprandial dose regimens of 50, 100, and 200 mg spironolactone were investigated in 45 outpatients with primary hypertension, WHO (World Health Organization) Stage I-II. Each of the three active therapy periods, which were randomly allocated to patients, were of 2 months' duration, with intervening placebo periods, Clinical and biochemical parameters, including furosemide-stimulated plasma renin activity (PRA), were recorded at regular intervals. All three spironolactone doses resulted in statistically significant blood pressure (BP) reductions independent of initial pretreatment levels and yielded satisfactory BP control in more than half of the patients. The 200 mg daily dose of spironolactone was found to be more effective than 50 but not 100 mg. When, correlating blood pressure response (delta MAP) to PRA, the profiling for positive spironolactone responders was characterized by high age and low PRA, irrespective of sex. Spironolactone therapy resulted in decreased serum sodium and magnesium values; potassium, creatinine, urate, and triglyceride levels were increased. However, all treatment values were within normal ranges. Side effects were infrequent and mainly of endocrine nature.

Prognostic factors for the course of beta cell function in autoimmune diabetes.

This study presents a 2-yr follow-up of 281 patients, aged 15-34 yr, diagnosed with diabetes between 1992 and 1993. At diagnosis, 224 (80%) patients were positive for at least one of the following autoantibodies: islet cell antibodies (ICAs), glutamic acid decarboxylase antibodies (GADAs), or tyrosine phosphatase antibodies (IA-2As); the remaining 57 (20%) patients were negative for all three autoantibodies. At diagnosis, C-peptide levels were lower (0. 27; 0.16-0.40 nmol/L) in autoantibody-positive patients compared with autoantibody-negative patients (0.51; 0.28-0.78 nmol/L; P: < 0. 001). After 2 yr, C-peptide levels had decreased significantly in patients with autoimmune diabetes (0.20; 0.10-0.37 nmol/L; P: = 0. 0018), but not in autoantibody-negative patients. In patients with autoimmune diabetes, a low initial level of C-peptide (odds ratio, 2. 6; 95% confidence interval, 1.7-4.0) and a high level of GADAs (odds ratio, 2.5; 95% confidence interval, 1.1-5.7) were risk factors for a C-peptide level below the reference level of 0.25 nmol/L 2 yr after diagnosis. Body mass index had a significant effect in the multivariate analysis only when initial C-peptide was not considered. Factors such as age, gender, levels of ICA or IA-2A or insulin autoantibodies (analyzed in a subset of 180 patients) had no effect on the decrease in beta-cell function. It is concluded that the absence of pancreatic islet autoantibodies at diagnosis were highly predictive for a maintained beta-cell function during the 2 yr after diagnosis, whereas high levels of GADA indicated a course of decreased beta-cell function with low levels of C-peptide. In autoimmune diabetes, an initial low level of C-peptide was a strong risk factor for a decrease in beta-cell function and conversely high C-peptide levels were protective. Other factors such as age, gender, body mass index, levels of ICA, IA-2A or IAA had no prognostic importance.

Enhancement of the bioavailability of propranolol and metoprolol by food.

The possible influence of food intake on the bioavailability of one nonselective and one cardioselective beta adrenoceptor antagonist, propranolol and metoprolol, was examined by serial determinations of the drug concentrations in blood of healthy subjects, taking single doses of the drugs both on an empty stomach and together with a standardized breakfast. The results indicate that food enhances the bioavailability of both propranolol and metoprolol. They also confirm that there is extensive interindividual variation in the bioavailability of these drugs.

Enhancement by food of canrenone bioavailability from spironolactone.

The influence of food intake on the bioavailability of canrenone, the major and active metabolite of spironolactone, was explored in 8 healthy male volunteers. Spironolactone was administered as a single oral dose of 100 mg, both in the fasting state and together with a standardized breakfast. Numerous venous blood samples were taken from 30 min to 96 hr after ingestion of the drug, and the plasma concentrations of canrenone were determined by spectrofluorometry. The results indicate that more canrenone enters the general circulation when spironolactone in ingested together with a meal.

Enhancement of hydralazine bioavailability by food.

The influence of food on the bioavailability of hydralazine in noncoated and coated tablets was examined in 5 healthy males. Each subject received an oral 50-mg dose on four different occasions: two 25-mg noncoated tablets with and without food and one 50-mg coated tablet with and without food. The meal was a standardized breakfast of 440 calories. Venous blood samples were obtained during a 6-hr period, and the plasma concentrations of unmetabolized hydralazine were assessed by a selective and sensitive gas chromatographic method. The results indicate that food enhances the bioavailability of hydralazine 2- to 3-fold both when noncoated and coated tablets are used.

Dietary fiber decreases fasting blood glucose levels and plasma LDL concentration in noninsulin-dependent diabetes mellitus patients.

Realistic high-fiber and regular low-fiber diets were given for 8 wk each to noninsulin-dependent diabetes mellitus (NIDDM) patients whose diabetes was being controlled satisfactorily by diet alone. The purpose of the study was to evaluate the metabolic effects of dietary fiber without changing energy intake or proportions of protein, fat, and carbohydrates. The high-fiber diet induced lower fasting blood glucose levels (p less than 0.01) and decreased the ratio of low-density lipoproteins to high-density lipoproteins (p less than 0.025); no difference was found in HbA1c between the two diet periods. Continuous glucose monitoring also showed a difference in fasting glucose levels that remained after identical low-fiber test meals. The incremental glucose responses did not differ. The fasting and incremental postprandial levels of insulin, C-peptide, glucagon, and somatostatin did not change, whereas the mean triglyceride concentrations were lower after the high-fiber diet. The results suggest a beneficial effect of dietary fiber in the metabolic control of NIDDM.

The effects of smoking, hypertension and cardiovascular disease on the estimation of unscheduled DNA synthesis and covalent binding to DNA induced by N-acetoxy-2-acetylaminofluorene in resting human mononuclear leukocytes.

The levels of N-acetoxy-2-acetylaminofluorene (NA-AAF)-induced unscheduled DNA synthesis (UDS) and of NA-AAF binding to DNA have been determined in resting mononuclear leukocytes from individuals with various smoking habits, heart infarct patients and subjects diagnosed for hypertension. Age-matched and blood-pressure-controlled smokers (n = 99) had significantly elevated levels of NA-AAF-induced UDS and NA-AAF binding to DNA when compared to nonsmokers (n = 75) similarly corrected for age and blood pressure. Heart infarct patients without any history of risk factors, as well as diagnosed hypertensives with normalized blood pressure, were not significantly different from matched controls when assessed by the NA-AAF method. Our results support the theory that increased mutagen sensitivity is associated with smoking and high blood pressure but not with cardiovascular disease itself via some mechanism of genetic selection.

Hyperinsulinaemia and other metabolic disturbances in well-controlled hypertensive men and women: an epidemiological study of the Dalby population.

Hypertensive subjects who have received no treatment have been found to be hyperinsulinaemic in previous studies using different populations. The present study was carried out to further examine the metabolic disturbances in carefully treated hypertensive subjects [diastolic blood pressure (DBP) less than 90 mmHg] of both sexes from the Dalby population. Three hundred and ten subjects who had been hypertensive for more than 5 years [DBP 88.1 +/- 0.5 (mean +/- s.e.m.)] were compared with 288 normotensive controls, matched for sex and age and chosen from the same population. After an overnight fast and with no medication for 24 h, an oral glucose tolerance test was carried out. P-insulin and P-C-peptide were analysed and insulin sum (P-insulin at start + after 2 h of oral glucose tolerance test) and C-peptide sum were calculated. Insulin and C-peptide sums were higher (P less than 0.001) in the hypertensive than in the normotensive subjects; 0.69 +/- 0.03, 3.36 +/- 0.08 and 0.41 +/- 0.02, 2.74 +/- 0.06, respectively. The diagnosis of hypertension, not the attained blood pressure level, correlated with insulin and C-peptide sums in multivariate analyses; F-values 20.96 (n = 598; P less than 0.001) and 6.68 (P less than 0.01), respectively. Hypertensive subjects under treatment, using calcium antagonists as monotherapy (n = 21), did not differ in age or body mass index from other hypertensives, but they had lower values for insulin and C-peptide sums; 0.45 +/- 0.05 and 2.63 +/- 0.18. Angiotensin converting enzyme inhibitors were not frequently used for monotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Life style changes improve insulin resistance in hyperinsulinaemic subjects: a one-year intervention study of hypertensives and normotensives in Dalby.

OBJECTIVE: Insulin resistance and hyperinsulinaemia are, in some prospective studies, linked to an increased cardiovascular risk, at least in men. We tested the hypothesis that hyperinsulinaemia may be reduced by non-pharmacological methods independently of other cardiovascular risk factors. DESIGN: In a non-pharmacological intervention study for 1 year three groups of subjects (hypertensives as well as normotensives) were selected after stratification for insulin level at baseline. Half of the hyperinsulinaemic subjects were randomly assigned to active intervention with physical exercise and dietary regulation (HI-A group), the other half were followed passively during the study period (HI-P group). Normo-insulinaemics and hypo(low)-insulinaemics also underwent active intervention (NI-A and LI-A groups, respectively). SETTING: Primary health care in Sweden. RESULTS: During the 1-year follow-up subjects in the HI-A group reduced their weight, waist:hip ratio and systolic and diastolic blood pressure, as well as their low:high-density lipoprotein (LDL:HDL)-cholesterol ratio. Glucose levels before and during an oral glucose tolerance test did not change. However, plasma insulin and plasma-C-peptide decreased both in the fasting state and after 1 and 2 h of oral glucose tolerance testing. This decrease was independent of the previously mentioned reduction in weight, waist:hip ratio, blood pressure and LDL:HDL-cholesterol ratio. No reduction in insulin levels was seen in the HI-P, NI-A or LI-A groups, but in the HI-P group there was a slight decrease in fasting plasma-C-peptide levels. In the HI-A group dietary improvements were observed during the study period, with a reduction in energy intake, fat consumption and cholesterol intake. Fibre intake was increased. No major changes were seen in the HI-P group. CONCLUSIONS: We conclude that in hypertensive and normotensive subjects with hyperinsulinaemia insulin levels can be reduced by active non-pharmacological treatment for 1 year without altering glucose tolerance. This shows that insulin resistance may be lowered by non-pharmacological treatment, which may be of considerable importance, and not only for hypertensives.

Antihypertensive efficacy and side effects of three beta-blockers and a diuretic in elderly hypertensives: a report from the STOP-Hypertension study.

OBJECTIVE: To compare the blood pressure-lowering efficacy, the frequency of side effects and changes in laboratory values of three beta-blockers and a potassium-sparing diuretic combination in elderly hypertensive patients. DESIGN: The Swedish Trial in Old Patients with Hypertension (STOP-Hypertension) was a prospective, randomized, double-blind, multicentre trial comparing active antihypertensive treatment with placebo in patients aged 70-84 years. METHODS: The study group consisted of 1627 elderly hypertensive patients (mean +/- SD age 75.7 +/- 3.7 years; 37% males, 63% females). Supine and standing blood pressure, heart rate and side effects were recorded at each visit. Blood was drawn for routine analysis. The mean length of follow-up was 25 months (range 6-65). No patient was lost to follow-up. RESULTS: After 2-months' single-drug therapy, all four active drugs were found to be equally effective in reducing diastolic blood pressure (DBP). However, there were differences in their efficacy in reducing systolic blood pressure (SBP); the diuretic was significantly more effective than the beta-receptor blockers. The results of a series of multiple linear regression analyses showed that the observed differences in effect on SBP could not be explained by the different effects of the drugs on heart rate. More than two-thirds of the patients were given supplementary treatment, most of them already by the 2-month visit, after which there was no significant difference in blood pressure among the treatment regimens. The changes in laboratory values and in the prevalence of symptoms were minor for all four regimens. CONCLUSION: Metoprolol (controlled release), atenolol, pindolol and the combination hydrochlorothiazide + amiloride were equally effective as single drugs in reducing DBP. There were differences in their efficacy in reducing SBP, the diuretic being more effective than the beta-blockers. After addition of supplementary treatment (beta-blocker to diuretic, or vice versa) there were no significant differences in blood pressure reduction among the groups. The changes in laboratory values and in the prevalence of symptoms were minor for all active treatment regimens. Thus, the satisfactory effect on cardiovascular morbidity and mortality was not impaired by low tolerability of the drugs.

Comparison of antihypertensive treatments in preventing cardiovascular events in elderly diabetic patients: results from the Swedish Trial in Old Patients with Hypertension-2. STOP Hypertension-2 Study Group.

BACKGROUND: The benefits of treating hypertension in elderly diabetic patients, in terms of achieving reductions in cardiovascular morbidity and mortality, have been documented in several recent prospective trials. There has, however, been some controversy regarding the effect of different antihypertensive drugs on the frequency of myocardial infarction in this group of patients. DESIGN: STOP Hypertension-2 was a prospective, randomized, open trial with blinded endpoint evaluation. METHODS: We studied 6614 elderly patients aged 70-84 years; 719 of them had diabetes mellitus at the start of the study (mean age 75.8 years). Patients were randomly assigned to one of three treatment strategies: conventional antihypertensive drugs (diuretics or beta-blockers), calcium antagonists, or angiotensin converting enzyme (ACE) inhibitors. RESULTS: Reduction in blood pressure was similar in the three treatment groups of diabetics. The prevention of cardiovascular mortality was also similar; the frequency of this primary endpoint did not differ significantly between the three groups. There were, however, significantly fewer (P = 0.025) myocardial infarctions during ACE inhibitor treatment (n = 17) than during calcium antagonist treatment (n = 32; relative risk 0.51, 95% confidence interval 0.28-0.92); but a (non-significant) tendency to more strokes during ACE inhibitor treatment (n = 34 compared with n = 29; relative risk 1.16, 95% confidence interval 0.71-1.91). CONCLUSION: Treatment of hypertensive diabetic patients with conventional antihypertensive drugs (diuretics, beta-blockers, or both) seemed to be as effective as treatment with newer drugs such as calcium antagonists or ACE inhibitors.

Effects of antihypertensive therapy on kidney function in diabetic patients.

Diabetic nephropathy is one of the major long term complications responsible for mortality in diabetes mellitus. While strict metabolic control of diabetes probably has a positive influence on kidney disease, most evidence supports the view that the process leading to end-stage renal failure has become independent of the metabolic disturbances of diabetes, and that haemodynamic factors in established nephropathy have become the predominant causes of progression of renal damage. In particular, increased intraglomerular pressure is thought to play a crucial part in the development of diabetic nephropathy. Therefore, drugs that can reduce intraglomerular pressure are of interest in treatment of hypertension in diabetic patients. The angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce intraglomerular pressure in animal studies, and the use of these drugs to treat insulin-dependent diabetics with hypertension has produced a reduction in the rate of decline of glomerular filtration rate. Although some beta-blockers can also have beneficial effects on renal function, they may produce unwanted metabolic effects. Thus the ACE inhibitors seem to be the most suitable antihypertensive drugs for diabetic patients.

Appearance of islet cell autoantibodies after clinical diagnosis of diabetes mellitus.

Islet cell antibodies (ICA) and glutamic acid decarboxylase antibodies (GAD65Ab) are often present at diagnosis of insulin dependent diabetes mellitus (type I diabetes) and are supposed to decline in level and frequency during the first years of disease. We have analysed ICA and GAD65Ab at onset and after one year in 395 population based randomly selected 15-34 year old patients newly diagnosed with diabetes mellitus, to study how these autoantibodies persist, disappear and appear and their relation to C-peptide levels. Of the 395 samples 212 (54%) were positive for ICA, 250 (63%) were positive for GAD65Ab and 170 (43%) were positive for both. At follow up after one year, 27/183 (15%) of the ICA negative patients and 25/145 (17%) of the GAD65Ab negative patients had converted to positivity. Among the 103 patients negative for both ICA and GAD65Ab, 16 turned positive for one or both antibodies after one year. Patients converting to positivity for one or the other antibody after one year, had lower C-peptide levels after one year than patients who initially were and remained negative, supporting the hypothesis that these patients have a genuine type I diabetes. In conclusion, newly diagnosed patients may be negative for autoantibodies at diagnosis but develop these antibodies later on during the disease.