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Biomedical subjects

C Berne

Publications and source records attributed to C Berne.

At least 55 records · Page 3Linked to original sources
PubMed1999

Factors predicting clinical remission in adult patients with type 1 diabetes.

OBJECTIVES: To describe the course of clinical remission in adult patients (16-50 years of age) with type 1 diabetes and to identify factors predictive of the occurrence and length of remission. DESIGN: A retrospective cohort study. SUBJECTS: Sixty-two consecutive patients (43 men and 19 women) with new onset IDDM, 27 +/- 8 years at diagnosis and treated with multiple insulin injections from the beginning. SETTING: Department of Medicine, Uppsala University Hospital and Orebro Medical Centre, Sweden. MAIN OUTCOME MEASURES: Length and occurrence of remission (defined as maintenance of HbA1c < or = 6.5% and an insulin dosage of < or = 0.4 U kg-1 day-1 for a minimum of 1 month) in relation to nine biochemical and clinical factors at diagnosis. RESULTS: Sixty-one per cent of the patients entered remission. The duration of remission was longer in males than females (10 +/- 12 vs. 2 +/- 3 months; P < 0.01). Male gender, normal serum bicarbonate at onset and a short time of classic symptoms before onset were predictive markers (P < 0.01; P < 0.05 and P < 0.01, respectively) for longer duration of remission. Low serum bicarbonate levels at onset were associated with lower occurrence of remission. Blood glucose, body mass index (BMI), and age at diagnosis did not influence the occurrence or the duration of remission. CONCLUSIONS: In most adult patients with new onset of type 1 diabetes remission is induced when using multiple insulin injection therapy. Male patients seem particularly prone to remission, and the length and extent of beta-cell strain prior to diagnosis strongly influences its course.

Adolescent↗
PubMed1999

Insulin-mediated vasodilation and glucose uptake are independently related to fasting serum nonesterified fatty acids in elderly men.

OBJECTIVES: To investigate candidate predictors for insulin sensitivity in healthy elderly males, with special reference to the influence of insulin-mediated skeletal muscle blood flow and serum nonesterified fatty acids (NEFA). SUBJECTS: From the participants in a health survey of 70-year-old males, focusing on cardiovascular risk factors, a subgroup of 46 men was sampled. Only men who declared themselves healthy and without medication were included. INTERVENTIONS: Insulin sensitivity was measured with the euglycaemic hyperinsulinaemic clamp. Leg blood flow was measured before and during the clamp, using the Doppler ultrasound technique. RESULTS: Hyperinsulinaemia [steady-state plasma insulin 105(15) mU L-1] increased leg blood flow by 10% (P < 0.004). When tested in bivariate analysis incremental leg blood flow was only significantly related to the serum NEFA concentration (r = - 0.38, P < 0.01) amongst a number of measured variables. Insulin-mediated glucose disposal was related to body mass index (BMI) (r = -0.49, P = 0. 0006), waist/hip ratio (r = - 0.31, P = 0.036), NEFA (r = - 0.50, P = 0.0004) and heart rate (r = - 0.34, P = 0.02). In multivariate analysis only BMI and NEFA remained significantly related to whole-body glucose uptake. CONCLUSIONS: The study demonstrates that in elderly men BMI and fasting serum NEFA but not insulin-induced vasodilation are related to insulin sensitivity. High fasting levels of NEFA relate to both impaired insulin-mediated vasodilation and impaired glucose disposal, respectively. These two insulin actions were not interrelated, however, a finding which may indicate dissociated mechanisms.

Aged↗
PubMed1999

Plasma total homocysteine and cysteine in relation to glomerular filtration rate in diabetes mellitus.

BACKGROUND: The plasma concentrations of total homocysteine (tHcy) and total cysteine (tCys) are determined by intracellular metabolism and by renal plasma clearance, and we hypothesized that glomerular filtration is a major determinant of plasma tHcy and tCys. We studied the relationships between the glomerular filtration rate (GFR) and plasma tHcy and tCys in populations of diabetic patients with particularly wide ranges of GFR. METHODS: We measured GFR, urine albumin excretion rate (UAER), plasma tHcy, tCys, methionine, vitamin B12, folate, C-peptide, and routine parameters in 50 insulin-dependent diabetes mellitus (IDDM) and 30 non-insulin-dependent diabetes mellitus (NIDDM) patients. All patients underwent intensive insulin treatment and had a serum creatinine concentration below 115 micromol/liter. RESULTS: Mean plasma tHcy in diabetic patients (0.1 micromol/liter) was lower than in normal persons (11.1 micromol/liter, P = 0.0014). Mean plasma tCys in diabetic patients (266.1 micromol/liter) was also lower than in normal persons (281.9 micromol/liter, P = 0.0005). Seventy-three percent of the diabetic patients had relative hyperfiltration. Plasma tHcy and tCys were closely and independently associated with GFR, serum folate, and serum B12. However, plasma tHcy was not independently associated with any of the 22 other variables tested, including age, serum creatinine concentration, UAER, total daily insulin dose, and glycemic control. CONCLUSIONS: Glomerular filtration rate is an independent determinant of plasma tHcy and tCys concentrations, and GFR is rate limiting for renal clearance of both homocysteine and cysteine in diabetic patients without overt nephropathy. Declining GFR explains the age-related increase in plasma tHcy, and hyperfiltration explains the lower than normal mean plasma tHcy and tCys concentrations in populations of diabetic patients.

Adult↗
PubMed1999

Response of the pituitary-adrenal axis to hypoglycemic stress in women with the polycystic ovary syndrome.

The role of the adrenals in the polycystic ovary syndrome (PCOS) is debated. Both single steroid-converting enzyme abnormalities and increased adrenal activity have received support. The conventional Synacthen test using pharmacological doses of ACTH results in unphysiological levels of ACTH. Therefore, we used insulin-induced hypoglycemia (0.15 IU/kg BW) to asses the responses of ACTH, cortisol, pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone, progesterone, 17-hydroxyprogesterone, and androstenedione in 18 women with PCOS and in 17 normal women of similar age and body mass index. The blood glucose concentration at 30 min was 2 mmol/L or less in all women, i.e. well below the threshold of the hormonal counterregulatory response. The women with PCOS showed a lower ACTH response, expressed as the maximum increment above basal [mean (95% confidence interval): PCOS, 11.1 (6.9-15.3); controls, 19.9 (13.8-26) pmol/L; P < 0.05], but a quantitatively comparable [PCOS, 207.2 (148.5-266.5); controls, 167.1 (100.6-233.2) nmol/L; P = NS] and more prompt cortisol response than the controls (by chi2 test, P < 0.05), resulting in a higher molar ratio between the maximum increments of cortisol and ACTH [PCOS, 13.9 (8.7-19); controls, 8.8 (5.7-12); P < 0.05]. The women with PCOS did, however, show a more rapid decline in cortisol levels than the controls (P < 0.05 at 120 and 180 min). The responses of the androgens and intermediate adrenal steroids were similar in women with PCOS and controls. The findings suggest an adaptation to increased adrenal reactivity to endogenous ACTH in women with PCOS. Exposure to hypoglycemia as a model of stress was not followed by hypersecretion of adrenal androgens and revealed no signs of steroid enzyme disturbances in women with PCOS.

Adrenocorticotropic Hormone↗
PubMed1999

Peripheral atherosclerosis and serum lipoprotein(a) in diabetes.

OBJECTIVE: Serum lipoprotein(a) [Lp(a)] is strongly associated with atherosclerosis in nondiabetic individuals. To see if atherosclerosis is also associated with serum Lp(a) in both IDDM and NIDDM, we determined the correlation between the toe systolic blood pressure index (TSPI) and serum Lp(a) in tightly controlled diabetic patients without nephropathy. RESEARCH DESIGN AND METHODS: Cross-sectional study of 57 IDDM and 35 NIDDM patients. All patients had been under strict glycemic control for at least 6 months. The main outcome measure was TSPI of both lower extremities. In addition, we measured serum Lp(a) and other serum lipids, serum uric acid, total plasma homocysteine, plasma C-peptide, HbA1c, albumin excretion rate, glomerular filtration rate, BMI, abdominal fat distribution, left ventricular hypertrophy, probabilities for cardiovascular disease (CVD), and routine clinical parameters. RESULTS: TSPI was closely and independently related to serum Lp(a) in IDDM patients: R2 = 0.2999, partial P = 0.0005, and in NIDDM patients: R2 = 0.7326, partial P = 0.0030. TSPI was associated with symptoms of CVD. Median serum Lp(a) concentration was normal in IDDM (45 mg/l [range 10-870]) and NIDDM (72 mg/l [11-803]) patients. CONCLUSIONS: Systemic atherosclerosis measured as the degree of peripheral occlusive arterial disease is strongly associated with serum Lp(a) in both IDDM and NIDDM patients. Serum Lp(a), however, is normal in both types of diabetic patients. Thus, it is indicated that serum Lp(a) should be measured in diabetic patients when assessing their risk profile for atherosclerosis.

Arteriosclerosis↗
PubMed1999

Local vasodilatation with metacholine, but not with nitroprusside, increases forearm glucose uptake.

Insulin is known to increase blood flow in parallel to glucose uptake in skeletal muscle. However, it is not known if an increase in blood flow by itself is associated with an increase in glucose uptake in the absence of hyperinsulinemia. To investigate further this matter, the effect of increased blood flow on forearm glucose uptake was studied in the fasting state during intra-arterial infusions of two different vasodilators, metacholine and nitroprusside, in 19 hypertensive subjects. Both metacholine (4 microg/min) and nitroprusside (10 microg/min) increased resting forearm blood flow, measured by venous occlusion plethysmography, to a similar degree (180 % and 170 %, respectively, p<0.0001 for both). However, metacholine infusion increased the forearm glucose uptake from 2.0+/-0.9 (S.D.) during rest to 5.5+/-3.0 umol/min/100 ml tissue (p<0.0001), while no significant change in glucose uptake was seen during nitroprusside infusion (2.3+/-1.4 micromol/min/100 ml tissue). In conclusion, vasodilatation induced by metacholine, but not by nitroprusside, increased glucose uptake in the forearm of hypertensive patients. Thus, an increase in forearm blood flow does not necessarily improve glucose uptake in the forearm during the fasting state.

Adult↗
PubMed1998

A high prevalence of diabetes mellitus and impaired glucose tolerance in the Danagla community in northern Sudan.

The prevalence and associated factors of diabetes mellitus (DM) and impaired glucose tolerance (IGT) were studied in a tribal community with an apparently high diabetes prevalence. A sample of 724 subjects aged > or = 25 years was selected using a multi-stage cluster method and underwent a 75 g oral glucose tolerance test. The crude prevalence of DM and IGT were 8.3% (men 9.9%; women 7.5%) and 7.9% (men 4.1%; women 9.7%), respectively. Age-adjusted prevalence rates, according to the standard population of Segi, were 10.4% (95% CI 7.7-13.2) and 9.8% (95% CI 7.2-12.5) for DM and IGT, respectively. No urban/rural differences were found in the prevalence rates of DM and IGT. New cases (5.1%) were almost twice as common as previously known cases (3.2%). Family history of diabetes, obesity, and advanced age were associated with higher rates of diabetes. The results confirmed that diabetes is common in the Danagla community compared to other communities of northern Sudan. Varying environmental, nutritional, and genetic factors may contribute to this high prevalence. These findings will have profound impact on the health services for this community and the Sudan as a whole.

Adult↗
PubMed1998

Level of heteroplasmy for the mitochondrial mutation A3243G correlates with age at onset of diabetes and deafness.

The mitochondrial mutation A3243G has been shown to be associated with a syndrome of diabetes mellitus and sensorineural hearing loss. Using a solid-phase-based sequencing method we have investigated the relation between the proportion of mutant mitochondrial genomes and the time of disease onset among members of three families where the mutation segregates. A striking association was observed between the level of heteroplasmy and time of onset of disease, particularly hearing loss. Accordingly, this syndrome shares features of diseases caused by dynamic mutations in that variable transmission of the level of heteroplasmy between generations influences disease severity.

Adolescent↗
PubMed1998

Angiotensin II and the endocrine pancreas: effects on islet blood flow and insulin secretion in rats.

An intrinsic angiotensin system has been described in the pancreas, with angiotensin II specific receptors being present on both exocrine, endocrine and vascular cells. The aim of the present study was to evaluate the effects of angiotensin II on insulin secretion and blood flow regulation in the pancreas. Blood flows were determined with a microsphere technique. Infusion of angiotensin II induced a dose-dependent reduction in both whole pancreatic and islet blood flow, which was most pronounced in the former. Administration of enalaprilate, an inhibitor of angiotensin-converting enzyme, and saralasin, a nonselective angiotensin II receptor antagonist, preferentially increased islet blood flow. The effects of angiotensin II on insulin release were examined by measuring insulin concentrations in the effluents from isolated perfused pancreata. In these preparations, enalaprilate affected neither basal nor glucose-stimulated insulin release, whereas angiotensin II delayed the first phase of insulin release in response to glucose. The effect of angiotensin II was probably due to initial marked vasoconstriction. The retardation of insulin release could be avoided by adding angiotensin II to the perfusion medium 20 min before glucose administration, i. e. so that the vasoconstriction had disappeared when glucose-stimulation began. The present study suggests that the angiotensin-system is important in regulation of islet blood flow and points to a pivotal role of islet blood perfusion for an adequate insulin release.

Angiotensin II↗
PubMed1998

The effect of euglucaemic hyperinsulinaemia on forearm blood flow and glucose uptake in the human forearm.

Insulin-mediated stimulation of blood flow to skeletal muscle has been proposed to be of major importance for insulin-mediated glucose uptake. The aim of this study was to investigate the relative importance of blood flow and glucose extraction as determinants of insulin-mediated glucose uptake in the human forearm. Forearm blood flow (FBF), glucose extraction and oxygen consumption were evaluated for 100 min during the euglycaemic hyperinsulinaemic clamp (92 mU/l) in nine healthy subjects. FBF was measured by venous occlusion plethysmography. Forearm glucose uptake increased sevenfold during the hyperinsulinaemia (P<0.001). Forearm glucose extraction showed a minor increase during the first 10 min of hyperinsulinaemia, but the most marked increase took place between 10 and 20 min (+170%). Thereafter, only a minor further increase was seen. During the first 10 min of hyperinsulinaemia FBF was unchanged. Thereafter, FBF increased steadily to a plateau reached after 60 min (+50%, P<0.001). A close relationship between whole body glucose uptake and FBF was seen at the end of the clamp (r = 0.75, P<0.02), but at this time the relationship between whole body glucose uptake and forearm glucose extraction was not significant. The modest increase in O2 consumption seen at the beginning of the clamp (+19%) was not related to FBF during the early phase of the clamp. In conclusion, the early course of insulin-mediated glucose uptake in the human forearm was mainly due to an increase in glucose extraction. However, with time the insulin-mediated increase in blood flow increased in importance and after 100 min of hyperinsulinaemia FBF was the major determinant of glucose uptake.

Adult↗
PubMed1998

Is there a role for leptin in the endocrine and metabolic aberrations of polycystic ovary syndrome?

Immunoreactive serum leptin was analysed in 49 women with polycystic ovary syndrome (PCOS) distributed on a wide range of body mass index (BMI; kg/m2) and in 32 normally menstruating women with comparable age, BMI, physical activity and dietary habits. All women with PCOS had increased androgen concentrations and obese women with PCOS (BMI > or = 25, n=24) also showed decreased insulin sensitivity and a preferential accumulation of truncal-abdominal body fat. Anthropometric and hormonal variables, insulin sensitivity, and pancreatic beta-cell activity were investigated in all women. Percentage body fat was calculated using gender-specific regression equations based on skinfold measurements. Serum leptin concentrations were higher in obese than in non-obese women (P < 0.001), but did not differ between the women with PCOS and controls, nor did they differ between glucose intolerant and glucose tolerant, or hirsute and non-hirsute women with PCOS. Both groups showed strong correlations between serum leptin concentrations and percentage body fat, BMI, body fat distribution, fasting plasma insulin and C-peptide, early insulin secretion, the free androgen index (FAI), and the degree of insulin resistance. After correcting for percentage body fat, only the FAI in the women with PCOS remained significant (P < 0.05). However, in a multiple regression analysis with both percentage body fat and the FAI as independent variables, the FAI increased only minimally (2%) the explained variation in leptin concentrations. Thus, serum leptin concentrations are almost exclusively determined by the total amount of body fat, independent of its location, and do not confirm the hypothesis that leptin is involved in the development of the hormonal and metabolic abnormalities in the PCOS.

Adolescent↗
PubMed1998

High prevalence of polycystic ovaries and associated clinical, endocrine, and metabolic features in women with previous gestational diabetes mellitus.

The prevalence of polycystic ovaries, according to ultrasonography, and associated clinical, endocrine, and metabolic features were investigated in women with previous gestational diabetes mellitus (GDM). Thirty-four women with GDM 3-5 yr before the investigation and 36 controls with uncomplicated pregnancies, selected for similar age, parity, and date of delivery, were investigated. The women with previous GDM showed a higher prevalence of polycystic ovaries [14 of 34 (41%) vs. 1 of 36 (3%); P < 0.0001], hirsutism (P < 0.01), irregular menstrual cycles (P < 0.01), and a higher body mass index (BMI; P < 0.001) than the controls. Five women (15%) with previous GDM had developed manifest diabetes (excluded in comparisons of metabolic variables). After dividing the women with previous GDM into subgroups according to ovarian appearance, the 2 subgroups showed similar glucose tolerance and prevalence of diabetes, whereas the women with polycystic ovaries were younger (mean +/- SD, 33.3 +/- 1.4 vs. 38.2 +/- 1.1; P < 0.01), had higher truncal-abdominal/femoral fat ratio according to skin folds (P < 0.05), had higher concentrations of androstenedione (P < 0.01) and testosterone (P < 0.01), and had a higher LH/FSH ratio (P < 0.01), lower levels of GH (P < 0.01), higher levels of triglycerides (P < 0.05) and cholesterol (P < 0.05) in very low density lipoprotein, all independent of age and BMI, and had a higher prevalence of pregnancy-induced hypertension (50% vs. 15%; P < 0.05) during the index pregnancy compared with the women with normal ovaries. The group of women with GDM showed a lower early insulin release after glucose (i.v. glucose tolerance test) for their degree of insulin resistance (euglycemic hyperinsulinemic clamp) compared with controls (P < 0.05). In the two subgroups, insulin sensitivity was lower in the polycystic ovaries group, independent of BMI (P < 0.05), than in the group with normal ovaries. In conclusion, ultrasonographic, clinical and endocrine signs of polycystic ovary syndrome were much increased in women with a history of GDM. Compared with the women with normal ovaries and previous GDM, those with polycystic ovaries formed a distinct subgroup that may be more prone to develop various features of the insulin resistance syndrome. Both groups showed a similarly disturbed balance between beta-cell activity and insulin sensitivity, but in women with polycystic ovaries, insulin resistance may be the dominant component.

Adult↗
PubMed1998

Induction of beta-cell rest in type 1 diabetes. Studies on the effects of octreotide and diazoxide.

OBJECTIVE: To evaluate the inhibitory effects of octreotide and diazoxide on insulin secretion in patients with type 1 diabetes and measurable levels of circulating C-peptide. RESEARCH DESIGN AND METHODS: Diazoxide was given to six patients during a 7-day period (100 mg three times daily), followed by a 3-week washout. Subsequently, octreotide (50 micrograms, three times daily) was administered subcutaneously for 7 days. Pre- and post- prandial blood glucose and serum C-peptide concentrations were measured before medication (control) and on day 7 of each medication period. Glucagon-stimulated C-peptide was determined in the morning before medication and on the day after each treatment period. RESULTS: Diazoxide inhibited glucagon-stimulated C-peptide secretion (mean increment 0.08 nmol/l vs. 0.18 nmol/l, P < 0.05), whereas octreotide had no such effect. Both reduced the pre- and postprandial serum C-peptide concentrations (P < 0.05), octreotide being the more potent in this respect. A reduction in basal and meal-related blood glucose was observed during octreotide treatment, whereas the glucose concentrations tended to be higher during treatment with diazoxide than during the 24-h control period. CONCLUSIONS: The study indicates that the two drugs reduce insulin output by different mechanisms. Diazoxide inhibits hormonal release directly on the beta-cells, whereas octreotide exerts its effect indirectly, presumably by multiple actions on insulin sensitivity and insulin-releasing hormones. The results suggest that each drug is capable of inducing beta-cell rest in type 1 diabetes.

Adult↗
PubMed1998

Regression of left ventricular wall thickness during ACE-inhibitor treatment of essential hypertension is associated with an increase in insulin mediated skeletal muscle blood flow.

UNLABELLED: Left ventricular hypertrophy (LVH) has been associated with insulin resistance, a condition with an impaired insulin-mediated vasodilation in skeletal muscle. ACE-inhibitors have been reported to be superior to most other antihypertensive drugs in inducing a regression of LVH. In a double-blind study with parallel groups, 50 patients with essential hypertension were randomized to treatment with either fosinopril (20 mg o.d.) or atenolol (50 mg o.d.) for 12-16 weeks. Left ventricle wall thickness (LVWT, defined as the sum of interventricular septum and posterior wall), diastolic function (represented by the ratio between the E-wave and the A-wave of mitral blood flow) and femoral artery blood flow (FBF) were evaluated using ultrasonic measurements. FBF was measured at normoinsulinemia and after 2 h of euglycemic hyperinsulinemia. Before treatment, the insulin-induced increase in FBF was inversely related to the LVWT (r = -0.52, p < 0.02). The reduction in ambulatory 24-h SBP/DBP was 13/9 mmHg for fosinopril and 15/14 for atenolol, ambulatory DBP being significantly more reduced by atenolol (p = 0.03 for difference in treatment effect). However, only fosinopril treatment resulted in a significant reduction in LVWT (from 20.5 mm to 19.4 mm, p < 0.05). The degree of reduction in LVWT was related to the increase in FBF in the fosinopril group (r = -0.45, p < 0.05). For fosinopril (but not for atenolol), there was a positive relationship between the change in E/A ratio and the change in femoral artery stroke volume (r = 0.80, p < 0.01). CONCLUSION: Impaired insulin-induced stimulation of leg blood flow was related to an increased LVWT. Furthermore, during fosinopril treatment, regression of LVWT was associated with enhanced skeletal muscle blood flow during hyperinsulinemia. This indicates that impaired peripheral blood flow (and thereby increased afterload) may be a possible mechanism explaining the previously found association between insulin resistance and cardiovascular hypertrophy.

Adolescent↗
PubMed1998

Classification of newly-onset IDDIM and NIDDIM in subjects aged 25-45 years in Sudan.

OBJECTIVES: To investigate the ability of classifying diabetes mellitus with clinical and biochemical characteristics at diagnosis in 25-45 years old patients. DESIGN: We determined age, body mass index (BMI), ICA, fasting C-peptide and HbA1c at diagnosis, and after 4-27 months follow up, these variables were related to the type of treatment. SETTING: Omdurman Teaching Hospital, Sudan. SUBJECTS: Eighty-six consecutive newly diagnosed diabetic patients, according to WHO criteria, were included. RESULTS: At diagnosis, 27 patients (31.4%) were treated with insulin and 59 (68.6%) with diet and/or oral hypoglycaemic agents (OHA). Insulin-treated patients at diagnosis were younger, had lower BMI and higher HbA1c. In the non-insulin treated group at diagnosis, ICA-negative patients (n = 54) had higher fasting C-peptide (P < 0.05) than ICA-positive. The treatment was changed from insulin to diet and/or OHA in 17 patients, and to insulin in six patients. Patients who discontinued insulin had already at diagnosis higher BMI and higher fasting C-peptide concentration (P < 0.005 and P < 0.05, respectively) than patients remained on insulin. The positive predictive values for insulin treatment of ICA positivity, low fasting C- peptide, and low BMI were 90, 78 and 73%, respectively. The sensitivity, specificity and positive predictive values for these variables in concurrence were, respectively, 85, 92 and 69%. CONCLUSION: The clinical classification of newly- diagnosed young Sudanese patients was satisfactory. With regular follow up and early commencement of appropriate treatment, good glycaemic control is certainly attainable. BMI is potentially valuable for the clinical classification in such patients. ICA and fasting serum C-peptide facilitate the choice of insulin treatment, but cost is a limit to large-scale use of these tests.

Adult↗