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Biomedical subjects

T Jenssen

Publications and source records attributed to T Jenssen.

At least 19 recordsLinked to original sources

Routine coronary angiography in diabetic nephropathy patients before transplantation.

We evaluated the incidence of significant coronary artery stenoses (CAS), angina pectoris (AP), revascularization and associated risk factors in 155 consecutive diabetic nephropathy transplant candidates. Kidney and kidney-pancreas transplant candidates with diabetes for more than 10 years and/or retinopathy and/or biopsy verified diabetic nephropathy were included. The inclusion period was 1999-2004. Seventy-two percent of patients were male. Sixty-one percent had type 1 diabetes and 39% had type 2 diabetes and mean age was 46 years (+/-10) and 58 years (+/-11), respectively. History of heart disease was present in 34% of patients, 34% had cerebro-vascular and/or peripheral atherosclerotic disease, and 51% had neither. Fifty-five percent had a smoking history and 46% were on dialysis. Significant CAS was found in 45% of patients, of whom 17% had AP. No patients below 35 years of age had significant CAS (n = 11, p = 0.001). Revascularization was performed in 57% of patients with significant CAS. The only risk factor for significant CAS in multiple logistic regression was age (p = 0.046). Approximately half of the patients had significant CAS, and half of these underwent revascularization. Most patients with CAS did not have symptoms of myocardial ischemia. The data justify screening diabetic nephropathy transplant candidates with coronary angiography before transplantation.

Adult↗

The impact of early-diagnosed new-onset post-transplantation diabetes mellitus on survival and major cardiac events.

The impact of early-diagnosed new-onset post-transplantation diabetes mellitus (PTDM) on cardiovascular (CV) disease is not well described. The objectives of the present prospective single-center observational study were to assess the long-term effects of early-diagnosed new-onset PTDM on major cardiac events (MCE; cardiac death or nonfatal acute myocardial infarction) and patient survival. Diabetic status and CV risk factors were assessed in 201 consecutive renal allograft recipients 3 months after transplantation (baseline) during a period of 16 months (1995-96). Follow-up data until January 1, 2004 were obtained from the Norwegian Renal Registry. The 8-year (range 7-9 years) cumulative incidence of MCEs was 7% (nine out of 138) in recipients without diabetes, 20% (seven out of 35) in patients with new-onset PTDM and 21% (six out of 28) in patients with diabetes mellitus before transplantation (DM). Proportional hazards regression analyses (forward stepwise regression) revealed that patients with PTDM had an approximately three-fold increased risk of MCEs as compared with nondiabetic patients (hazard ratio (HR)=3.27, 95% confidence interval (CI)=1.22-8.80, P=0.019). A total of 61 patients (30%) died. Eight-year patient survival was 80% in the nondiabetic group, 63% in the PTDM group and 29% in the DM group, respectively. Pretransplant diabetes (HR=5.09, 95% CI=2.60-9.96, P<0.001), age (HR=1.03, 95% CI=1.01-1.05, P=0.016), cytomegalovirus (CMV) infection (HR=2.66, 95% CI=1.27-5.53, P=0.009), and creatinine clearance (HR=0.98, 95% CI=0.96-1.00, P=0.046), but not PTDM (HR=1.20, 95% CI=0.58-2.49, P=0.621), were independent predictors of death in the multiple Cox regression model. Early-diagnosed PTDM is a predictor of MCEs, but not of all-cause mortality, the first 8 years after renal transplantation.

Adult↗

Type 2 diabetic patients have increased gluconeogenic efficiency to substrate availability, but intact autoregulation of endogenous glucose production.

OBJECTIVE: An autoregulatory mechanism involving a reciprocal relationship between gluconeogenesis and glycogenolysis regulates endogenous glucose production (EGP) in healthy individuals. In type 2 diabetes, fasting hyperglycemia may be due to increased EGP. MATERIAL AND METHODS: To examine gluconeogenesis and autoregulation of EGP in type 2 diabetes, 9 type 2 diabetics and 8 healthy controls were studied during a 3-h infusion of 30 micromol/kg/min Na-lactate. The diabetics were also studied during a control infusion of Na-bicarbonate. To standardize levels of glucoregulatory hormones, plasma insulin, growth hormone, and glucagon were clamped at identical levels during the three experiments. Glucagon levels were elevated from basal levels to approximately 330 ng/l when the lactate or bicarbonate infusions were started, in order to mimic the hyperglucagonemia often seen in diabetes. Lactate gluconeogenesis and total EGP were measured by infusions of [6-(3)H] glucose and [U-14C] lactate. RESULTS: In the bicarbonate experiments, hyperglugagonemia increased lactate gluconeogenesis in the diabetic patients from 4.3+/-1.8 to 6.1+/-2.4 micromol/kg/min (p=0.04). EGP did not change significantly (basal EGP: 15.3+/-3.9, EGP at the end of the study: 14.2+/-3.9 micromol/kg/min, p=0.14). During both lactate experiments, plasma lactate increased more than 4-fold. The increase in lactate gluconeogenesis was significantly higher in diabetics than in controls (values obtained at the end of experiments minus basal values: 10.8+/-3.6 versus 6.4+/-3.6 micromol/kg/min, p=0.03). Compared with normal subjects, the diabetic patients had higher EGP values both at basal conditions (p=0.001) and during lactate infusion (p=0.005). Despite augmented gluconeogenesis, EGP did not change during lactate and glucagon infusion in any of the groups (diabetics, basal EGP: 15.4+/-2.7 versus EGP at the end of experiments: 15.6+/-3.6 micromol/kg/min, p>0.30. Controls, basal EGP: 11.8+/-0.8 versus EGP at the end of experiments: 11.6+/-1.9 micromol/kg/min, p>0.30). CONCLUSIONS: Although type 2 diabetics have increased EGP and increased lactate gluconeogenesis, the hepatic autoregulation of EGP during increased substrate-induced gluconeogenesis seems to be intact.

Adult↗

Asymptomatic cytomegalovirus infection is associated with increased risk of new-onset diabetes mellitus and impaired insulin release after renal transplantation.

AIMS/HYPOTHESIS: The human cytomegalovirus (CMV) may increase the risk of diabetes mellitus, but the literature is scarce. The present study was designed to test the hypothesis that asymptomatic CMV infection is associated with increased risk of new-onset diabetes after renal transplantation, and to assess the impact of asymptomatic CMV infection on OGTT-derived estimates of insulin release and insulin action. METHODS: A total of 160 consecutive non-diabetic renal transplant recipients on cyclosporine (Sandimmun Neoral)-based immunosuppression were closely monitored for CMV infection during the first 3 months after transplantation. All patients underwent a 75-g OGTT at 10 weeks. Excluded from the analyses were 36 patients with symptomatic CMV infection (disease). RESULTS: The incidence of new-onset diabetes was 6% in a control group of recipients without CMV infection (4/63) and 26% in the group with asymptomatic CMV infection (16/61). Asymptomatic CMV infection was associated with a significantly increased risk of new-onset diabetes (adjusted odds ratio: 4.00; 95% CI: 1.19 to 13.43, p=0.025). The group of patients with CMV infection had a significantly lower median insulin release than controls. CONCLUSIONS/INTERPRETATION: Our findings support the hypothesis that asymptomatic CMV infection is associated with increased risk of new-onset post-transplant diabetes mellitus, and suggest that impaired insulin release may involve one pathogenetic mechanism.

Antigens, Viral↗

The associations of endogenous testosterone and sex hormone-binding globulin with glycosylated hemoglobin levels, in community dwelling men. The Tromsø Study.

OBJECTIVES: Low levels of endogenous testosterone have been associated with increased risk of cardiovascular disease and atherosclerosis in men. Long-term hyperglycemia, as measured by glycosylated hemoglobin (HbA1c), is related to cardiovascular mortality, and HbA1c across its normal range is also positively related to coronary heart and cardiovascular disease mortality in men. We therefore undertook an analysis of the cross-sectional associations of total testosterone and SHBG levels with HbA1c levels, in a general population of 1419 men aged 25-84. METHODS: Total testosterone, sex hormone-binding globulin (SHBG) and HbA1c were measured by immuno-assay. Partial correlation and multiple regression analyses were used to estimate the associations between total testosterone and SHBG with HbA1c. Analyses of variance and covariance were used to compare men with or without diabetes. RESULTS: In age-adjusted partial correlation HbA1c was inversely associated with total testosterone (p<0.01) and SHBG (p<0.001). HbA1c was positively associated with body mass index (BMI) and waist circumference (WC) (p<0.001). In multiple regression analyses total testosterone, SHBG, age, number of cigarettes smoked, BMI and WC were independently associated with HbA1c levels. Men with a history of diabetes had lower levels of total testosterone in age-adjusted analyses (p<0.05) and lower levels of SHBG in both age- and WC-adjusted analyses (p<0.001 and p<0.01, respectively). CONCLUSION: Lower levels of total testosterone and SHBG were associated with increased HbA1c levels and diabetes independent of concomitant variations in obesity and body fat distribution.

Adult↗

Insulin resistance after renal transplantation: impact of immunosuppressive and antihypertensive therapy.

OBJECTIVE: The purpose of the present study was to validate various surrogate estimates of insulin sensitivity (IS) in a renal transplant population and to assess the influence of immunosuppressive and antihypertensive therapy on insulin resistance (IR) after renal transplantation. RESEARCH DESIGN AND METHODS: A total of 167 consecutive renal transplant recipients without previously known diabetes underwent a 75-g oral glucose tolerance test (OGTT) 3 months after renal transplantation. A total of 43 patients also underwent a euglycemic-hyperinsulinemic glucose clamp study. Six OGTT-derived IS indexes were validated against the euglycemic-hyperinsulinemic glucose clamp-derived IS index (ISI(CLAMP)). RESULTS: The OGTT-derived ISI(TX) correlated closely with the ISI(CLAMP) (r = 0.58, P < 0.001). The other surrogate estimates of IS were also significantly but less well correlated with the ISI(CLAMP) (Spearman's correlation; r = -0.45 to 0.41, P = 0.003-0.050). In the univariate model, BMI, daily prednisolone dose, creatinine clearance, hypertension, number of antihypertensive agents, and use of diuretics or beta-blockers were negatively associated with ISI(TX) (P < 0.05). After multiple regression analysis, BMI (P < 0.001), daily prednisolone dose (P < 0.001), cytomegalovirus infection (P = 0.030), and triglycerides (P = 0.034) were shown to be independent predictors of posttransplant IR. CONCLUSIONS: The OGTT-derived ISI(TX) may be a useful estimate of IS in Caucasian renal transplant recipients. Increasing daily prednisolone dose is an independent predictor of IR after renal transplantation. Hypertension and the use of beta-blockers and diuretics may also deteriorate IR in this group of patients.

Adolescent↗

[Prevention of cardiovascular disease in type 2 diabetes].

BACKGROUND: Patients with type 2 diabetes have a high risk of morbidity and premature mortality from cardiovascular disease. Epidemiological studies show that many of the risk factors are the same as in non-diabetic subjects. At present there are sufficient data in the literature to recommend prophylactic measures to be initiated in diabetic patients. MATERIAL AND METHODS: We review major studies relevant for prophylactic measures against cardiovascular disease in patients with type 2 diabetes, and suggest Norwegian recommendations. RESULTS: All patients should be advised to adhere to a healthy life style including an appropriate diet, physical exercise and no smoking. Treatment of hyperglycaemia is primarily indicated in order to improve quality of life and reduce the risk of microvascular complications, as it still remains to be proven if glucose lowering therapy may protect against macrovascular disease. Pharmacological prophylactic therapy with acetylsalicylic acid, anti-hypertensive agents and lipid lowering drugs are indicated in high-risk patients. IMPLICATIONS: Several pharmacological and non-pharmacological interventions may protect type 2 diabetic patients from premature cardiovascular morbidity and mortality. Anti-hypertensive treatment may protect diabetic patients both from microvascular and macrovascular disease and premature death.

Antihypertensive Agents↗

[New diagnostic criteria for diabetes mellitus--why?].

In 1997, the diagnostic criteria for diabetes mellitus were changed in the USA; the WHO has also proposed changes in its criteria. The main difference from the previous set of WHo criteria is a lowering of the cut-off level of fasting plasma glucose to > or = 7.0 mmol/l. This article discusses the implications of new diagnostic criteria and recommends that the level of fasting plasma glucose for diagnosing diabetes is decreased to > or = 7.0 mmol/l in Norway as well.

Blood Glucose↗

Relative conributions of beta-cell function and tissue insulin sensitivity to fasting and postglucose-load glycemia.

We performed hyperglycemic clamps in 283 nondiabetic Caucasians and, with multiple linear regression, determined the contribution of beta-cell function and tissue insulin sensitivity to variations in glycemia and insulinemia during oral glucose tolerance tests (OGTTs). Impaired glucose tolerance (IGT) subjects had reduced insulin sensitivity (P < .02) and beta-cell function (P < .0001). Normal glucose tolerance (NGT) subjects with first-degree type 2 diabetic relatives had reduced first and second phase insulin secretion (both, P < .05), but normal insulin sensitivity (P = .37). Beta-Cell function and insulin sensitivity accounted for one fourth of the variability in glucose tolerance. Fasting plasma glucose in subjects with NGT (n = 185) was a function of both phases of insulin secretion and of insulin sensitivity (all, P < .05), whereas, in IGT subjects (n = 98), it was a function of first phase insulin secretion and insulin sensitivity (P < .01). Two-hour glycemia was a function of second phase secretion and insulin sensitivity (P < .01). Fasting and 2-hour plasma insulin levels were determined by insulin sensitivity (and glycemia) in NGT subjects (P < .001), but by second phase secretion in IGT (P < .001). We conclude that beta-cell function is reduced in subjects with IGT; glycemia and insulinemia are not regulated by the same mechanisms in IGT and NGT; insulin sensitivity does not contribute to insulinemia in IGT; family history of diabetes influences beta-cell function, but not insulin sensitivity in Caucasians.

Adult↗

Plasma beta-endorphin concentrations are increased in chronic obstructive pulmonary disease patients.

The present study is concerned with plasma beta-endorphin and glucose tolerance in patients with chronic obstructive pulmonary disease (COPD). Plasma beta-endorphin, glucagon and insulin concentrations were measured during an oral glucose tolerance test in 20 COPD patients and in 18 age-matched healthy controls (mean age 62 years). Seven patients had a moderate COPD (group I) and seven a severe COPD (group II). The remaining six severe COPD patients received long-term oxygen therapy (group III). We found that fasting levels of beta-endorphin were significantly increased in all patient groups compared to healthy controls (p < 0.01, 0.05 and 0.005, respectively). Six of the 13 severely diseased COPD patients had impaired glucose tolerance. Plasma beta-endorphin levels decreased significantly during OGTT in the COPD patients (p < 0.05). Fasting beta-endorphin levels were higher in patients with impaired glucose tolerance than in those patients with normal OGTT (42.0 pmol/L +/- 11.4 SD versus 34.8 +/- 10.2). However, this difference was not statistically significant. In conclusion, this study showed that beta-endorphin concentrations are increased in COPD patients whether or not they receive oxygen therapy.

Blood Glucose↗

Intracerebral abscess caused by Nocardia otitidiscaviarum in a renal transplant patient--cured by evacuation plus antibiotic therapy.

We present a 50-year-old female who experienced generalized convulsion 3 months after a successful cadaveric renal transplantation. The first cerebral CT scan indicated cerebral frontal infarction. Repeat CT some days later revealed progressive lesions, and a highly malignant tumor or abscess was suspected. Antifungal and broad-spectrum antibacterial therapy was initiated. Cerebral MRI could not differentiate between these conditions, but a neutrophil granulocyte scan strongly suggested an infectious process. A stereotactic puncture of the frontal lobe was followed by temporary improvement. A severe progressive left-sided hemiparalysis gave indication for a craniotomy with evacuation of the abscess 9 days later. Culture of aspirated pus yielded growth of a gram-positive, rod-shaped bacterium, later identified as Nocardia otitidiscaviarum by sequencing the 16S rRNA. The patient was treated with meropenem plus rifampicin intravenously for 6 weeks followed by oral ciprofloxacin and rifampicin for 2 months. Due to pharmacokinetic interaction with rifampicin, the prednisolone dose was doubled, and the dose of tacrolimus had to be tripled for maintenance of adequate trough concentrations. Five months following cessation of antibiotic treatment, the patient has regained normal strength and function in her left-sided extremities and has a serum creatinine level of about 160 micromol/l (1.8 mg/dl).

Anti-Bacterial Agents↗

Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity.

OBJECTIVE: The oral glucose tolerance test (OGTT) has often been used to evaluate apparent insulin release and insulin resistance in various clinical settings. However, because insulin sensitivity and insulin release are interdependent, to what extent they can be predicted from an OGTT is unclear. RESEARCH DESIGN AND METHODS: We studied insulin sensitivity using the euglycemic-hyperinsulinemic clamp and insulin release using the hyperglycemic clamp in 104 nondiabetic volunteers who had also undergone an OGTT. Demographic parameters (BMI, waist-to-hip ratio, age) and plasma glucose and insulin values from the OGTT were subjected to multiple linear regression to predict the metabolic clearance rate (MCR) of glucose, the insulin sensitivity index (ISI), and first-phase (1st PH) and second-phase (2nd PH) insulin release as measured with the respective clamps. RESULTS: The equations predicting MCR and ISI contained BMI, insulin (120 min), and glucose (90 min) and were highly correlated with the measured MCR (r = 0.80, P < 0.00005) and ISI (r = 0.79, P < 0.00005). The equations predicting 1st PH and 2nd PH contained insulin (0 and 30 min) and glucose (30 min) and were also highly correlated with the measured 1st PH (r = 0.78, P < 0.00005) and 2nd PH (r = 0.79, P < 0.00005). The parameters predicted by our equations correlated better with the measured parameters than homeostasis model assessment for secretion and resistance, the delta30-min insulin/delta30-min glucose ratio for secretion and insulin (120 min) for insulin resistance taken from the OGTT. CONCLUSIONS: We thus conclude that predicting insulin sensitivity and insulin release with reasonable accuracy from simple demographic parameters and values obtained during an OGTT is possible. The derived equations should be used in various clinical settings in which the use of clamps or the minimal model would be impractical.

Blood Glucose↗

Population-based study of the relationship among muscle morphology, insulin action, and hypertension.

To examine whether changes in muscle morphology are linked to the metabolic abnormalities associated with the insulin resistance syndrome, muscle morphology and the metabolic profile were examined in 52 individuals with untreated hypertension (mean arterial pressure [MAP] = 117+/-7 mm Hg) and 38 carefully matched controls (MAP = 89+/-5 mm Hg). Oral glucose tolerance tests and hyperglycemic clamps were performed for measurements of insulin action on glucose disposal and suppression of nonesterified fatty acids (NEFA). Fully automated, computer-aided techniques were used for morphometric measurements of muscle biopsies from m. vastus lateralis. The hypertensive and normotensive groups did not differ in insulin sensitivity to glucose disposal (0.18+/-0.16 v. 0.19+/-0.13 micromol/kg/min/pmol/L; P = .20) and NEFA suppression (87.5+/-7.3 v. 87.2+/-9.4%, P>0.30) during a hyperglycemic clamp. The groups were similar in the proportion of types 1, 2a, and 2b muscle fibers, fiber size, and capillary density. Fiber roundness (ratio of fiber perimeter squared to fiber area) differed in the hypertensive (1.51+/-0.07) and normotensive (1.58+/-0.12, P = .004) groups, showing that the muscle fibers in the hypertensive group were more rounded in shape, a nonspecific change often seen after minimal ischemic lesions. The quotient expressing fiber roundness was associated with systolic (r = -0.29, P = .01) and diastolic (r = -0.32, P = .005) blood pressure. We conclude that persons with mild and moderate hypertension do not have abnormalities in muscle morphology that could explain the impairment of insulin action often observed in this condition. However, hypertensive individuals have increased muscle fiber roundness. It is wondered whether hypertension may be a condition with defects in the regulation of the transmembranous ion transport, leading to raised intracellular sodium concentration, swelling of the cytoplasma, and roundening of the fibers.

Adult↗