Glucose metabolism in patients with psoriasis.

BACKGROUND: Epidemiological studies strongly suggest that psoriasis predisposes to type 2 diabetes. Several theories have been proposed to explain how these disease entities might be pathophysiologically connected. OBJECTIVES: Our primary objective was to elucidate whether clinical data support the notion of common pathophysiological denominators in patients with psoriasis and type 2 diabetes, and thus to delineate the association between the two conditions that has arisen on the basis of epidemiological studies. METHODS: We reviewed clinical studies investigating parameters of glucose metabolism in patients with psoriasis. The PubMed and Embase databases were searched for studies investigating glucose metabolism in adult patients with psoriasis as a primary or secondary end point. Studies had to include a relevant control group. RESULTS: Twenty-six clinical studies reporting on insulin resistance, glucose tolerance or insulin secretion were eligible for review. The results were widely conflicting, with less than half of the studies showing results suggestive of defective glucose metabolism in patients with psoriasis. In general, the studies suffered from a lack of information regarding possible confounders and patient characteristics. Furthermore, the research methods varied, and in all but one study they might not have been appropriate to detect early and subtle defects in glucose metabolism. CONCLUSIONS: The available literature does not unequivocally support common pathophysiological denominators in psoriasis and type 2 diabetes. Well-designed clinical studies are needed to expose potential diabetogenic defects in the glucose metabolism in patients with psoriasis.

Near-normalization of glycaemic control with glucagon-like peptide-1 receptor agonist treatment combined with exercise in patients with type 2 diabetes.

AIMS: To investigate the effects of exercise in combination with a glucagon-like peptide-1 receptor agonist (GLP-1RA), liraglutide, or placebo for the treatment of type 2 diabetes. METHODS: Thirty-three overweight, dysregulated and sedentary patients with type 2 diabetes were randomly allocated to 16 weeks of either exercise and liraglutide or exercise and placebo. Both groups had three supervised 60-minute training sessions per week including spinning and resistance training. RESULTS: Glycated haemoglobin (HbA1c) levels dropped by a mean ± standard deviation of 2.0% ± 1.2% (from 8.2% ± 1.4%) in the exercise plus liraglutide group vs 0.3% ± 0.9% (from 8.0% ± 1.2%) in the exercise plus placebo group ( P < .001), and body weight was reduced more with liraglutide (-3.4 ± 2.9 kg vs -1.6 ± 2.3 kg; P < .001). Compared with baseline, similar reductions were seen in body fat (exercise plus liraglutide: -2.5% ± 1.4% [ P < .001]; exercise plus placebo: -2.2% ± 1.9% [ P < .001]) and similar increases were observed in maximum oxygen uptake (exercise plus liraglutide: 0.5 ± 0.5 L O2 /min [ P < .001]; exercise plus placebo: 0.4 ± 0.4 L O2 /min [ P = .002]). Greater reductions in fasting plasma glucose (-3.4 ± 2.3 mM vs -0.3 ± 2.6 mM, P < .001) and systolic blood pressure (-5.4 ± 7.4 mm Hg vs -0.6 ± 11.1 mm Hg, P < .01) were seen with exercise plus liraglutide vs exercise plus placebo. The two groups experienced similar increases in quality of life during the intervention. CONCLUSIONS: In obese patients with type 2 diabetes, exercise combined with GLP-1RA treatment near-normalized HbA1c levels and caused a robust weight loss when compared with placebo. These results suggest that a combination of exercise and GLP-1RA treatment is effective in type 2 diabetes.

At least one in three people with Type 2 diabetes mellitus referred to a diabetes centre has symptomatic obstructive sleep apnoea.

AIMS: To investigate the prevalence of symptomatic obstructive sleep apnoea in unselected patients with Type 2 diabetes referred to a tertiary diabetes clinic. METHODS: In a cross-sectional design, all newly referred patients were offered a stepwise screening for obstructive sleep apnoea with: (1) The Berlin questionnaire; then, if indicative: (2) overnight home monitoring with the ApneaLink™ device. Patients with an apnoea-hypopnoea index ≥ 5/h were offered referral for diagnostic polygraphy and treatment initiation. RESULTS: A total of 200 patients participated (61% men; age 59.6 ± 10.5 years, diabetes duration 8.3 ± 6.3 years and BMI 31.7 ± 6.7 kg/m²). According to the questionnaire, 106 patients showed 'high risk' of obstructive sleep apnoea, and 72 of these were referred to polygraphy based on ApneaLink screening corresponding to a prevalence of symptomatic obstructive sleep apnoea of 39%. Patients with symptomatic obstructive sleep apnoea had significantly higher BMI, poorer glycaemic control and lower plasma HDL cholesterol levels as compared with patients unlikely to have obstructive sleep apnoea. The groups were not different with respect to sex, age, diabetes duration, blood pressure, diabetic complications or medication use. In multiple regression analyses, age, BMI and HDL cholesterol levels were all significant, independent predictors of obstructive sleep apnoea. CONCLUSIONS: At least one third of people with Type 2 diabetes referred to a diabetes clinic in Denmark has symptomatic obstructive sleep apnoea. Our data suggest higher age, a compromised plasma lipid profile and a more obese phenotype in patients with Type 2 diabetes who have obstructive sleep apnoea, highlighting the need to focus on screening and treatment of obstructive sleep apnoea in these patients.

Decreased protein levels of key insulin signalling molecules in adipose tissue from young men with a low birthweight: potential link to increased risk of diabetes?

AIMS/HYPOTHESIS: Individuals with low birthweight are at increased risk of type 2 diabetes mellitus. However, the underlying molecular mechanisms are unknown. Previously we have shown that low birthweight is associated with changes in muscle insulin signalling proteins. Here we determined whether low birthweight is associated with changes in insulin signalling proteins in adipose tissue. METHODS: Men (age 23 years) with either a low (bottom 10th percentile) (n = 17) or a normal (50th-90th percentile) (n = 17) birthweight were recruited from the Danish Medical Birth Registry and subcutaneous adipose biopsies were taken. RESULTS: Between the two groups there was no difference in protein level of the insulin receptor, protein kinase C zeta, glycogen synthase kinase-3 (GSK3) alpha, GSK3 beta, protein kinase B alpha and beta, peroxisome proliferative activated receptor gamma coactivator 1 or Src-homology-2-containing protein. However, the levels of GLUT4 (also known as solute carrier family 2 [facilitated glucose transporter], member 4 [SLC2A4]) (52 +/- 10.9% reduction, p < 0.01), p85alpha subunit of phosphoinositide 3-kinase (PI3K) (45 +/- 9% reduction, p < 0.01), p110ss subunit of PI3K (48 +/- 17% reduction, p = 0.06) and IRS1 (59 +/- 24% reduction, p < 0.05) were reduced in men of low birthweight. CONCLUSIONS/INTERPRETATION: These findings show that low birthweight is associated with reduced levels of adipose insulin signalling proteins, thus providing a potential molecular framework to explain why people with low birthweight are at increased risk of developing type 2 diabetes. These differences precede the development of diabetes and thus may help predict disease risk.

Consequences of low birthweight on urinary excretion of DNA markers of oxidative stress in young men.

OBJECTIVE: Low birthweight (LBW) has been associated with an increased risk of development of type 2 diabetes in adult life. Both type 1 and type 2 diabetes mellitus are characterized by increased oxidative stress. The purpose of this study was to investigate whether young healthy adults born with LBW showed differences in oxidative stress under normal conditions and during the added challenge of a physiological Intralipid infusion. MATERIAL AND METHODS: Urinary excretion of DNA markers of oxidative stress were analyzed by LC-MS/MS in 19 men (aged 19 years) with LBW and in 19 age matched, normal birthweight (NBW) controls pre- and post a 3-fold increase of plasma free fatty acids. RESULTS: Mean excretion rates of 8-oxo-guanine (8oxoGua), 8-oxo-guanosine (8oxoGuo), 8-oxo-2'deoxyguanosine (8oxodG), and 1,N6-ethenodeoxyadenosine (epsilon dA) did not statistically differ between subjects with LBW and NBW (66.9 versus 73.9 nmol/15 h, 17.8 versus 18.5 nmol/15 h, 11.9 versus 14.4 nmol/15 h and 44.0 versus 43.2 pmol/15 h, respectively). Furthermore, Intralipid infusion did not affect excretion of DNA adducts in LBW or NBW subjects. Statistically significant correlations were found between body mass index and urinary excretion of 8oxoGua (r = 0.64, p = 0.003) and 8oxoGuo (r = 0.64, p = 0.003) in the LBW group only. CONCLUSIONS: These findings suggest that oxidative stress may be a consequence of diabetes and is not, or at least only partly, involved in the early pathogenesis of type 2 diabetes.

Low birthweight is associated with specific changes in muscle insulin-signalling protein expression.

AIMS/HYPOTHESIS: People with low birthweight have an increased risk of developing type 2 diabetes mellitus in adulthood. The mechanistic basis of this phenomenon is not known. Here we investigate the effect of early growth restriction on the expression of insulin-signalling proteins in skeletal muscle in a human cohort and a rat model. METHODS: We recruited 20 young men with low birthweight (mean birthweight 2702+/-202 g) and 20 age-matched control subjects (mean birthweight 3801+/-99 g). Biopsies were obtained from the vastus lateralis muscle and protein expression of selected insulin-signalling proteins was determined. Rats used for this study were male offspring born to dams fed a standard (20%) protein diet or a low (8%) protein diet during pregnancy and lactation. Protein expression was determined in soleus muscle from adult offspring. RESULTS: Low-birthweight subjects showed reduced muscle expression of protein kinase C (PKC)zeta, p85alpha, p110beta and GLUT4. PKCzeta, GLUT4 and p85 were also reduced in the muscle of rats fed a low-protein diet. Other proteins studied were unchanged in low-birthweight humans and in rats fed a low-protein diet when compared with control groups. CONCLUSIONS/INTERPRETATION: We found decreased expression of specific insulin-signalling proteins in low-birthweight subjects compared to controls. These changes precede the onset of impaired glucose tolerance. The similarity of protein expression profile in the men with low birthweight compared to that of the offspring of rats fed a low-protein diet suggests that the rodent model is an accurate representation of the human situation. It also provides a potential mechanistic explanation as to why the fetal environment plays an important role in determining risk of developing type 2 diabetes.

Effect of taurine treatment on insulin secretion and action, and on serum lipid levels in overweight men with a genetic predisposition for type II diabetes mellitus.

BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) is increasing with an epidemic growth rate. Animal studies with taurine supplementation have shown increased insulin secretion and action, suggesting that taurine supplementation may have a potential to prevent T2DM. OBJECTIVE: To assess the effect of taurine treatment on insulin secretion and action, and on plasma lipid levels in overweight men with a positive history of T2DM. DESIGN: 20 nondiabetic subjects were included in a double-blinded, randomized, crossover study, receiving a daily supplementation of 1.5 g taurine or placebo for two periods of 8 weeks. The subjects were overweight first-degree relatives of T2DM patients. An intravenous glucose tolerance test (IVGTT) was used to measure first-phase insulin secretory response, and a euglycemic hyperinsulinemic clamp was used to determine peripheral insulin action. RESULTS: Mean plasma taurine concentration was 39 +/- 7 (s.d.) micromol/l after placebo and 131 +/- 62 micromol/l after taurine intervention (P < 0.0001). There was no significant difference after taurine intervention compared to placebo in incremental insulin response (Insincr.) neither during the IVGTT, nor in insulin-stimulated glucose disposal during the clamp. Insulin secretion, adjusted for insulin sensitivity, was also unchanged. There was no significant effect of taurine supplementation on blood lipid levels as well. CONCLUSION: Daily supplementation with 1.5 g taurine for 8 weeks had no effect on insulin secretion or sensitivity, or on blood lipid levels. These findings in persons with an increased risk of T2DM are in contrast to those from animal studies, and do not support the assumption that dietary supplementation with taurine can be used to prevent the development of T2DM.

Normal insulin-stimulated endothelial function and impaired insulin-stimulated muscle glucose uptake in young adults with low birth weight.

Low birth weight has been linked to insulin resistance and cardiovascular disease. We hypothesized that insulin sensitivity of both muscle and vascular tissues were impaired in young men with low birth weight. Blood flow was measured by venous occlusion plethysmography during dose-response studies of acetylcholine and sodium nitroprusside in the forearm of fourteen 21-yr-old men with low birth weight and 16 controls of normal birth weight. Glucose uptake was measured during intraarterial insulin infusion. Dose-response studies were repeated during insulin infusion. The maximal blood flow during acetylcholine infusion was 14.1 +/- 2.7 and 14.4 +/- 2.1 [ml x (100 ml forearm)(-1) x min(-1)] in low and normal birth weight subjects, respectively. Insulin coinfusion increased acetylcholine-stimulated flow in both groups: 18.0 +/- 3.1 vs. 17.9 +/- 3.1 [ml x (100 ml forearm)(-1) x min(-1)], NS. Insulin infusion increased glucose uptake significantly in the normal birth weight group, compared with the low birth weight group: 0.40 +/- 0.09 to 1.00 +/- 0.16 vs. 0.44 +/- 0.09 to 0.59 +/- 0.1 [ micro mol glucose x (100 ml forearm)(-1) x min(-1)], P = 0.04. Young men with low birth weight have normal insulin-stimulated endothelial function and impaired insulin-stimulated forearm glucose uptake. Thus, endothelial dysfunction does not necessarily coexist with metabolic alterations in subjects with low birth weight.

Insulin signal transduction in skeletal muscle from glucose-intolerant relatives of type 2 diabetic patients [corrected].

To determine whether defects in the insulin signal transduction cascade are present in skeletal muscle from prediabetic individuals, we excised biopsies from eight glucose-intolerant male first-degree relatives of patients with type 2 diabetes (IGT relatives) and nine matched control subjects before and during a euglycemic-hyperinsulinemic clamp. IGT relatives were insulin-resistant in oxidative and nonoxidative pathways for glucose metabolism. In vivo insulin infusion increased skeletal muscle insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation (P = 0.01) and phosphatidylinositide 3-kinase (PI 3-kinase) activity (phosphotyrosine and IRS-1 associated) in control subjects (P < 0.02) but not in IGT relatives (NS). The incremental increase in insulin action on IRS-1 tyrosine phosphorylation was lower in IGT relatives versus control subjects (P < 0.05). The incremental defects in signal transduction noted for IRS-1 and PI 3-kinase may be attributed to elevated basal phosphorylation/activity of these parameters, because absolute phosphorylation/activity under insulin-stimulated conditions was similar between IGT relatives and control subjects. Insulin increased Akt serine phosphorylation in control subjects and IGT relatives, with a tendency for reduced phosphorylation in IGT relatives (P = 0.12). In conclusion, aberrant phosphorylation/activity of IRS-1, PI 3-kinase, and Akt is observed in skeletal muscle from relatives of patients with type 2 diabetes with IGT. However, the elevated basal activity of these signaling intermediates and the lack of a strong correlation between these parameters to glucose metabolism suggests that other defects of insulin signal transduction and/or downstream components of glucose metabolism may play a greater role in the development of insulin resistance in skeletal muscle from relatives of patients with type 2 diabetes.

Prevalence of alcohol problems among adult somatic in-patients in Naples.

The aim of this cross-sectional study was to determine the prevalence of alcohol problems among adult somatic in-patients in urban hospitals of Naples. The patients were screened with a structured questionnaire regarding life style. After discharge, the patient records were examined and the hospital discharge diagnoses were registered. A patient was considered having an alcohol problem if one or more of the following criteria were fulfilled: (1) a Michigan Alcoholism Screening Test score at or above five; (2) a self-reported daily consumption for at least 2 years of at least 60 g of ethanol for males and 36 g for females; (3) an alcohol-related discharge diagnosis. The prevalence of patients with alcohol problems was significantly (P < 0.01) higher among male (43.8%, 95% confidence limits, 37.6-50.2%) than among female patients (14.8%, 95% confidence limits, 9.6-21.4%). There were no significant differences among the different types of somatic departments regarding the prevalence of alcohol problems when gender was considered. Patients with alcohol problems differed significantly from those without alcohol problems regarding a number of variables: the former drank significantly more alcohol, smoked for more years, and had a higher prevalence of alcohol problems in the family. It is concluded that alcohol problems among in-patients are as prevalent in Naples as in other industrialized countries, that it is often not registered among discharge diagnoses, and that the problems are more prevalent in males than in females, irrespective of the type of department.

The validity of the Michigan Alcoholism Screening Test (MAST).

This review examines the validity of the Michigan Alcoholism Screening Test (MAST) as a screening instrument for alcohol problems. Studies that compare the MAST-questionnaire with other defined diagnostic criteria of alcohol problems were retrieved through MEDLINE and a cross-bibliographic check. A total of 20 validity studies were included. The studies varied considerably regarding the prevalence of alcohol problems, the diagnostic criteria, and the examined patient categories. The MAST compared with other diagnostic criteria of alcohol problems gave validity measures with the following span: predictive positive value (PVpos) 0.24-0.96, predictive negative value (PVneg) 0.78- approximately 1, sensitivity 0.36- approximately 1, and specificity 0.36-0.96. It appears that the PVneg are high. Except from one study, the sensitivities (0.57- approximately 1) are also high. The PVpos and the specificities show substantial variations. The variables that seem to have the largest influence on the PVpos seem to be the prevalence of alcohol problems, the diagnostic method against which the MAST-questionnaire is validated, and the populations on which the MAST is applied. The MAST should in the future be validated against internationally accepted diagnostic methods on populations with representative prevalences of alcohol problems.

Prevalence of alcohol problems among adult somatic in-patients of a Copenhagen hospital.

The adult patients of somatic departments of a Copenhagen hospital were screened on a randomly selected day during a 14 day period by interviewers who examined them using a structured questionnaire regarding life-style. A patient was considered having an alcohol problem if one or more of the following criteria was fulfilled: (1) a self-reported daily alcohol consumption for at least 2 years of at least 60 g of ethanol in men and 36 g in women, (2) a Michigan Alcoholism Screening Test (MAST) score of or above 5, (3) an alcohol-related discharge diagnosis. In total, 692 patients fulfilled the entry criteria, but 181 patients (26.2%) had to be excluded owing to predefined exclusion criteria (terminal illness, dementia, etc.), and 74 patients (14.5%) refused to participate. Among the 437 interviewed patients, 125 patients (28.6%; 95%-confidence limits 24.4-33.1%) fulfilled one or more of the diagnostic criteria for an alcohol problem. Only 14 patients (3.2%; 95%-confidence limits 1.8-5.3%) had an alcohol-related discharge diagnosis. The prevalence of patients with alcohol problems was significantly (P < 0.05) higher among male patients (82 of 171 men (48.0%; 95%-confidence limits 40.3-55.7%)) than among female patients (43 of 266 women (16.2%; 95%-confidence limits 12.0-21.2%)). The prevalence of patients with alcohol problems was 32.4% (95%-confidence limits 25.5-39.8%) in internal medicine departments, 28.5% (95%-confidence limits 21.3-36.6%) in surgical departments, and of female patients 22.2% (95%-confidence limits 13.7-32.8%) in the department of gynaecology and obstetrics.