Major stressful life events in relation to prevalence of undetected type 2 diabetes: the Hoorn Study.

OBJECTIVE: To test whether chronic psychological stress is positively associated 1) with the prevalence of type 2 diabetes; 2) with visceral adiposity; and to test whether 3) the relationship between stress and diabetes is mainly mediated by visceral adiposity RESEARCH DESIGN AND METHODS: In a general Caucasian population aged 50-74 years without a history of diabetes (n = 2,262), the number of major stressful life events experienced during the past 5 years was assessed by self-report before the administration of an oral glucose tolerance test. RESULTS: Diabetes was newly diagnosed among 5% of the subjects. The number of stressful events was positively associated with the prevalence of hitherto undetected diabetes. The highest quintile had a 1.6-fold (95% CI 1.0-2.6) increased probability of undetected diabetes compared with the remaining four quintiles (P<0.05 by logistical regression analysis adjusted for age and sex). This increased probability remained significant after additional adjustment for family history of diabetes, heavy alcohol consumption, physical activity, and low level of education. The number of stressful events was weakly positively associated with waist-to-hip ratio (WHR) (men, P<0.01; women, P = 0.05 by multiple regression analysis adjusted for age). The age- and sex-adjusted association between stress and diabetes was only marginally reduced by adding the WHR into the logistical regression model (odds ratio 1.5 [0.9-2.4]; P = 0.08). CONCLUSIONS: These cross-sectional findings are partially consistent with Björntorp's theory that stressful life events, which indicate chronic psychological stress, are indeed associated with undetected type 2 diabetes and with visceral adiposity. However, in this white middle-aged population, visceral adiposity does not seem to be the main link between stress and diabetes.

Prevalence and determinants of glucose intolerance in a Dutch caucasian population. The Hoorn Study.

OBJECTIVE: To study the prevalence and determinants of glucose intolerance in a general Caucasian population. RESEARCH DESIGN AND METHODS: A random sample of 50- to 74-year old Caucasians (n = 2,484) underwent oral glucose tolerance tests. Multiple regression analyses were performed to study the association of 2-h postload plasma glucose values with potential determinants. RESULTS: Prevalence of known and newly detected diabetes and impaired glucose tolerance was 3.6, 4.8, and 10.3%, respectively. In women, but not in men, the association of body mass index with 2-h glucose was fully accounted for by the waist-to-hip ratio. Maternal history of diabetes was twice as prevalent as paternal history, but paternal history only was associated with 2-h glucose. In addition, paternal history was a stronger determinant in men than in women. An independent positive association with 2-h plasma glucose was found for alcohol use of > 30 g/day in women and for intake of total protein, animal protein, and polyunsaturated fatty acids in men. An independent inverse association with 2-h plasma glucose was demonstrated for height (both sexes), alcohol use of < or = 30 g/day (both sexes), energy intake (in men), and, unexpectedly, current smoking (in men). CONCLUSIONS: The prevalence of diabetes in elderly Caucasians was 8.3%. In men, dietary habits may unfavorably influence glucose tolerance independent of obesity.

Leptin and variables of body adiposity, energy balance, and insulin resistance in a population-based study. The Hoorn Study.

OBJECTIVE: Leptin is thought to play a key role in the control of body weight. There is a complex interrelationship between leptin and insulin or insulin resistance, but it is unknown how leptin is regulated. We therefore explored, in a large population-based study of 2,484 Caucasian subjects aged 50-74 years, the relationship between leptin and variables of body adiposity, energy balance, and insulin resistance. RESEARCH DESIGN AND METHODS: Leptin was measured by means of a radioimmunoassay. Multiple linear regression analyses were performed with leptin as dependent variable and age, sex, BMI, waist circumference, daily energy intake, physical activity, smoking, hypertension, fasting triglyceride concentrations, HDL cholesterol, fasting plasma glucose, and fasting plasma insulin concentrations as independent variables (determinants) RESULTS: Leptin concentrations were found to be four times higher in women than in men. Effect modification between sex and potential determinants was expected, and the analyses were performed separately for women and men. BMI was the strongest determinant of leptin in women and waist circumference the strongest determinant in men. BMI, waist circumference, insulin, and triglyceride concentrations were independently and significantly (P < 0.05) associated with leptin, while inverse associations were shown for smoking and daily energy intake (borderline significance). CONCLUSIONS: This study confirms the relationship between insulin and leptin and, in addition, suggests a relationship between triglyceride concentrations and leptin independent of sex, BMI, waist circumference, and insulin.

The effects of verapamil and propranolol on exercise tolerance in hypertensive patients.

In a single-blind, placebo-controlled crossover study the effects of verapamil (450 +/- 30 mg/day) and propranolol (160 +/- 20 mg/day) on endurance time during submaximal exercise were compared in eight patients with essential hypertension. The drugs were given in randomized order. Each active drug period was preceded by a placebo phase. Endurance tests were performed during both placebo periods and treatment with verapamil and propranolol by bicycle ergometry. Both drugs were equally effective in decreasing resting blood pressure. Verapamil and propranolol reduced exercise heart rate, the effect of propranolol being more pronounced. With placebo, endurance time during exercise was 57 +/- 11 minutes; with propranolol it was 32 +/- 7 minutes (P less than 0.05). Verapamil had no influence on endurance time. The study demonstrates that in contrast to propranolol, verapamil has no influence on exercise tolerance during submaximal work in patients with hypertension.

A long-term study of plasma catecholamine levels and plasma renin activity in borderline hypertension.

Blood pressure and plasma catecholamine levels were followed up for a total of 7 years in 26 subjects with borderline hypertension and in 24 normotensive subjects. During the observation period, five subjects from the borderline hypertensive group became definitely hypertensive, 10 remained in the borderline hypertensive range and in 10, blood pressure fell below borderline hypertensive levels. Of the original 24 normotensive subjects, 15 remained in the normotensive range. In seven, blood pressure rose, but did not reach borderline hypertensive levels. Three subjects were lost to follow-up. In contrast with the subjects who remained normotensive and borderline hypertensive, those who became definitely hypertensive had consistently high plasma noradrenaline concentrations at rest. Plasma adrenaline levels and plasma noradrenaline concentrations during exercise did not differ, however. The study suggests that borderline hypertensive subjects who develop definite hypertension within a few years have consistently enhanced sympathetic activity.

Dissimilar association of conventional immuno-reactive versus specific insulin with cardiovascular risk factors: a consequence of proinsulinaemia?

In this study involving 365 non-diabetic elderly Caucasians, we examined the relationship of immuno-specific insulin (ISI), total immuno-reactive insulin (IRI), proinsulin (PI) and proinsulin-insulin ratio (PI:ISI) to serum high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), systolic blood pressure (SBP) and diastolic blood pressure (DBP), mean blood pressure (MBP) and pulse pressure. In a multiple regression analysis, adjusted for age, sex and obesity, a 1.3-fold stronger inverse association with HDL-C levels was found for IRI than for ISI, with a 1.6-fold better fit of the regression equation. The positive association of insulin with TG was 1.6-fold stronger for IRI compared to ISI, with a 2.5-fold better fit. In contrast, the positive association of IRI with the various blood pressure parameters was 1.5-1.9-fold weaker than for ISI, with a 2.1-3.8-fold worse fit. Both PI:ISI ratio and PI were independently associated with TG levels, but not with HDL-C. The PI:ISI ratio but not PI, was associated with blood pressure, but dependent on glycaemia. In conclusion, compared to ISI, IRI overestimates the association of insulin with serum lipids and underestimates the association of insulin with blood pressure. The use of non-specific insulin assays may explain the inconsistencies in the findings of previous epidemiological studies.

Combined surgical and endovascular treatment of a giant vertebral artery aneurysm in a child. Case report.

The case is presented of a 5-year-old child who suffered a subarachnoid hemorrhage from a giant left vertebral artery-posterior inferior cerebellar artery (PICA) aneurysm. Initial treatment consisted of surgical occlusion of the parent vertebral artery combined with a PICA-to-PICA bypass. Because of persistent filling of the aneurysm, the left PICA was occluded at its takeoff from the aneurysm. Endovascular coil occlusion of the aneurysm and the distal left vertebral artery enabled complete elimination of the aneurysm. Follow-up magnetic resonance imaging and arteriography performed 6 months postoperatively showed persistent occlusion and elimination of the mass effect. Combined surgical bypass and endovascular occlusion of the parent artery may be a useful adjunct in the management of these aneurysms.

Computer-assisted health impact assessment for intersectoral health policy.

Intersectoral health policy implies negotiations with politicians outside the health sector. Health politicians have a stronger position if they can quantify health impact. In this Dutch case-study we used a computer simulation approach to answer the following questions: Which anti-tobacco intervention has the largest health gain? Will a commuter cycling policy result in any substantial health gain? What is the relative health gain of promoting higher consumption of vegetables and fruit? We concluded that substantial health gain can be achieved if cigarette packet price were to increase by 2 Dutch guilders. A commitment of all general practitioners to implement a smoking cessation intervention will result in a similar health gain. Stimulating commuter cycling could be a promising example of intersectoral health policy. Interventions to promote higher vegetable and fruit consumption will result in a relatively small health gain. Pros and cons of simulation models to support intersectoral health policy are discussed.

Hearing loss in a uraemic patient: indications of involvement of the VIIIth nerve.

A case of acute renal failure associated with severe uraemic hearing loss is presented. Audiometric site-of-lesion testing revealed cochlear as well as neural involvement. After therapy hearing recovered up to an almost normal level, with normal auditory nerve conduction velocities. This case report supports the suggestion that the improvement of hearing after renal transplantation or dialysis might be correlated with the influences of these forms of therapy upon the peripheral neuropathy.

The use of calcium antagonists in patients with renal failure.

Calcium antagonists are now frequently used for the treatment of high blood pressure, angina pectoris and cardiac arrhythmias. Increasingly, these drugs are also given to patients with renal failure, since several studies have demonstrated that calcium antagonists lower blood pressure in patients with renal hypertension and renal insufficiency. Relevant pharmacokinetic parameters for verapamil, nitrendipine and diltiazem are not altered in renal failure. The situation is more complex in the case of nifedipine. However, studies with repeated administration have demonstrated that the calcium antagonists verapamil, diltiazem, nifedipine and nitrendipine can be given in the same doses to patients with renal failure as to patients with normal renal function.

Impaired glucose tolerance and unidentified diabetes.

The epidemiology of impaired glucose tolerance and undiagnosed non-insulin-dependent diabetes mellitus is reviewed and the implications for screening strategies discussed.

New data on the rate of progression of impaired glucose tolerance to NIDDM and predicting factors.

The Hoorn study has investigated the prevalence of impaired glucose tolerance (IGT) and diabetes in a random sample of the population, 50-75 years of age, in the small Dutch town of Hoorn. The percentage of the population identified as having IGT was 10.3%, while 8.4% had diabetes. The prevalence of both diabetes and IGT was higher in older subjects (70-74 years of age) than in younger subjects (50-54 years of age), suggesting that age is a major determinant of the prevalence of IGT and diabetes in a population. A prospective study of the development of non-insulin dependent diabetes mellitus (NIDDM) in the subjects identified as having IGT was then initiated. Preliminary results for the 158 subjects who have been followed for a mean of 2 years indicated that 28.5% (95% confidence interval, 15-42%) have progressed to NIDDM within this period. The progression rate calculated from this value is 13.8%/year (95% confidence interval, 3.5-24%/year). Analysis of possible determinants of conversion has revealed that 2-hour plasma glucose levels greater than 9.4 mmol/litre and increased fasting proinsulin levels are predictive of progression to NIDDM. This suggests that beta cell dysfunction, rather than increased insulin resistance, is responsible for the development of NIDDM.

Pharmacokinetics of nitrendipine in terminal renal failure.

The pharmacokinetics and plasma protein binding of nitrendipine in patients with terminal renal failure have been compared with those in subjects with normal renal function. Kinetic parameters were calculated after a single 40 mg oral dose, an i.v. injection of 3 mg and after a 15 mg i.v. infusion of nitrendipine. Steady-state plasma levels were determined after 5 days of oral treatment with 20 mg b.d. Pharmacokinetic parameters and steady-state plasma levels in patients with renal failure did not differ from those in subjects with normal renal function. Nitrendipine was as highly bound to plasma proteins in patients with renal failure, as in subjects with normal renal function. The plasma protein did not differ between the two. The dosage of nitrendipine need not be modified for kinetic reasons in patients with renal failure.

Chronic granulocytic leukemia in a renal transplant recipient.

Chronic granulocytic leukemia developed four years after renal transplantation in a patient, who had been treated with immunosuppressive agents since then. The low incidence of leukemia in comparison with malignant lymphoma in renal transplant recipients and some pathogenetic mechanisms are discussed.

Influence of prolonged submaximal exercise on the pharmacokinetics of verapamil in humans.

The influence of prolonged submaximal exercise on the pharmacokinetics of verapamil was studied in normal volunteers both after i.v. injections of 0.13 mg/kg body weight as well as after one oral dose of 80 mg of the calcium entry blocker. Each dose was given on a rest day and on an exercise day. On the rest day, the terminal phase half-life (t1/2) of verapamil averaged 161 +/- 23 min after i.v. injection of the drug. The total clearance was 772 +/- 125 ml/min, and the area volume of distribution was 198 +/- 53 L. These parameters were not altered on the exercise day. Neither did exercise have any influence on the pharmacokinetic parameters determined after oral application of verapamil. This study shows that prolonged submaximal exercise has no influence on the pharmacokinetics of verapamil.