Mitochondrial Complex I Inhibition by Metformin: Drug-Exercise Interactions.

Metformin has antidiabetic, anticancer, and prolongevity effects, but seems to interfere with aerobic training mitochondrial adaptations. The primary mechanism of action has been suggested to be the inhibition of mitochondrial complex I. Recent papers (Wang et al. and Cameron et al.), however, provide evidence to deny the hypothesis of a direct action of metformin on complex I.

Hypoglycaemic episodes in patients with type 2 diabetes--risk factors and associations with patient-reported outcomes: The PANORAMA Study.

AIM: To explore the frequency of hypoglycaemic episodes, their risk factors, and associations with patient-reported outcomes in patients with type 2 diabetes enrolled in the PANORAMA cross-sectional study. METHODS: Five thousand seven hundred and eighty-three patients aged ≥ 40 years with type 2 diabetes duration ≥ 1 year were recruited in nine European countries. Patients reported severe and non-severe hypoglycaemic episodes during the past year at a single study visit. Patient-reported outcomes were measured by the Audit of Diabetes-Dependent Quality of Life, Diabetes Treatment Satisfaction Questionnaires, Hypoglycaemia Fear Survey-II, and EQ-5D Visual Analog Scale. RESULTS: During the previous year, 4.4% of the patients experienced ≥ 1 severe hypoglycaemic episode; among those without severe hypoglycaemia, 15.7% experienced ≥ 1 non-severe episode. Patients experiencing any hypoglycaemic episode reported a greater negative impact of diabetes on quality of life, greater fear of hypoglycaemia, less treatment satisfaction and worse health status than those with no episodes. In multivariate analyses hypoglycaemia was significantly associated with longer diabetes duration; presence of microvascular and, to a lesser extent, macrovascular complications; treatment with insulin, glinides or sulfonylureas; and use of self-monitoring blood glucose. CONCLUSION: In patients with type 2 diabetes, severe hypoglycaemic episodes were not uncommon and one in five experienced some form of hypoglycaemia during the previous year. Hypoglycaemia was associated with more negative patient-reported outcomes. The risk of hypoglycaemia increased with diabetes duration, presence of diabetes-related complications, use of self-monitoring blood glucose, insulin secretagogues, and insulin treatment.

Comparison of insulin glargine and liraglutide added to oral agents in patients with poorly controlled type 2 diabetes.

AIM: To compare safety and efficacy of insulin glargine and liraglutide in patients with type 2 diabetes (T2DM). METHODS: This randomized, multinational, open-label trial included subjects treated for T2DM with metformin ± sulphonylurea, who had glycated haemoglobin (HbA1c) levels of 7.5-12%. Subjects were assigned to 24 weeks of insulin glargine, titrated to target fasting plasma glucose of 4.0-5.5 mmol/L or liraglutide, escalated to the highest approved clinical dose of 1.8 mg daily. The trial was powered to detect superiority of glargine over liraglutide in percentage of people reaching HbA1c <7%. RESULTS: The mean [standard deviation (s.d.)] age of the participants was 57 (9) years, the duration of diabetes was 9 (6) years, body mass index was 31.9 (4.2) kg/m(2) and HbA1c level was 9.0 (1.1)%. Equal numbers (n = 489) were allocated to glargine and liraglutide. Similar numbers of subjects in both groups attained an HbA1c level of <7% (48.4 vs. 45.9%); therefore, superiority of glargine over liraglutide was not observed (p = 0.44). Subjects treated with glargine had greater reductions of HbA1c [-1.94% (0.05) and -1.79% (0.05); p = 0.019] and fasting plasma glucose [6.2 (1.6) and 7.9 (2.2) mmol/L; p < 0.001] than those receiving liraglutide. The liraglutide group reported a greater number of gastrointestinal treatment-emergent adverse events (p < 0.001). The mean (s.d.) weight change was +2.0 (4.0) kg for glargine and -3.0 (3.6) kg for liraglutide (p < 0.001). Symptomatic hypoglycaemia was more common with glargine (p < 0.001). A greater number of subjects in the liraglutide arm withdrew as a result of adverse events (p < 0.001). CONCLUSION: Adding either insulin glargine or liraglutide to subjects with poorly controlled T2DM reduces HbA1c substantially, with nearly half of subjects reaching target levels of 7%.

Isoinertial and isokinetic sprints: muscle signalling.

To determine if the muscle signalling response to a 30 s all-out sprint exercise is modulated by the exercise mode and the endocrine response, 27 healthy volunteers were divided in 2 groups that performed isokinetic (10 men and 5 women) and isoinertial (7 men and 5 women) Wingate tests. Blood samples and vastus lateralis muscle biopsies were taken before, immediately after, 30 and 120 min after the sprints. Groups were comparable in age, height, body weight, percentage of body fat, peak power per kg of lower extremities lean mass (Pmax) and muscle fibre types. However, the isoinertial group achieved a 25% greater mean power (Pmean). Sprint exercise elicited marked increases in the musculus vastus lateralis AMPKα, ACCß, STAT3, STAT5 and ERK1/2 phosphorylation (all P<0.05). The AMPKα, STAT3, and ERK1/2 phosphorylation responses were more marked after the isoinertial than isokinetic test (interaction: P<0.01). The differences in muscle signalling could not be accounted for by differences in Pmax, although Pmean could explain part of the difference in AMPKα phosphorylation. The leptin, insulin, glucose, GH, IL-6, and lactate response were similar in both groups. In conclusion, the muscle signalling response to sprint exercise differs between isoinertial and isokinetic sprints.

Blood pressure, antihypertensive treatment and factors associated with good blood pressure control in hypertensive diabetics: the Tarmidas study.

Numerous population studies confirm the high prevalence of hypertension in type II diabetic (DM2) subjects and that intensive antihypertensive treatment is more beneficial to diabetic than to nondiabetic hypertensive subjects, yet not many of these are specific to Spain. To assess the degree of blood pressure (BP) control and the effects of antihypertensive drugs in the medical management of hypertension in diabetic patients in specialist care centres throughout Spain, we studied the socio-demographic, clinical and relevant laboratory parameters of 796 hypertensive patients with DM2 (mean age 66.09 (95% confidence interval (CI): 64.08-68.10). The percentage of diabetic patients responding positively to BP control measures was lower when compared to the nondiabetic population in both Spain and Europe. The degree of control was poorer for systolic than for diastolic BP, yet 40.6% of the patients were only on monotherapy. The fact that antihypertensive treatment was modified in only 40% of the poorly controlled patients was also highly significant and could be attributed to a nonstringent use of clinical guidelines. Among the other differences between well-controlled and poorly controlled patients, we found that well-controlled patients presented with lower levels of cholesterol and triglycerides, a lower prevalence of excess weight/obesity, and a greater prevalence of cardiovascular and/or cerebrovascular disease despite having a greater percentage of patients on antiplatelet therapy. Better application of therapeutic guidelines and the prevention and treatment of compounding factors could improve the response rate to BP control measures in poorly controlled patients.

Patterns of prescription of hypoglycaemic drugs in Gran Canaria (Canary islands, Spain) and estimation of the prevalence of diabetes mellitus.

OBJECTIVE: To study the patterns of hypoglycaemic treatment in our community and to estimate the prevalence of known and drug-treated diabetes mellitus. METHODS: From all the diabetic patients who attended the Healthcare Centers of the National Health Service in Gran Canaria in 1999, a random sample of 2924 diabetic patients > 20 years old was selected. Data on age, gender, clinical onset of diabetes, and hypoglycaemic treatment were obtained. Data on drug consumption were supplied by the National Health Service. RESULTS: Of the DM-2 patients 4.4% (3.65-5.14) 84.2% (82.7785.42), 9.4% (8.34-10.45) and 2.1% (1.58-2.61) received diet only, oral drugs, insulin or combination. The duration of DM-2 was associated with more oral drugs and more insulin treatment, but the duration of DM-1 was not associated with intensive insulin therapy;<50% of the type 1 patients had >or=3 daily injections. The prescriptions of biguanides were scarce; over 1/3 of them were of buformin. DM-1 and DM-2 patients were treated with similar doses of insulin, but DM-1 patients had more insulin injections (2.56 vs 2.07, P<0.001), and more fast-acting insulins (65.2% vs 38.0%, P<0.001). The estimated prevalences of known and drug-treated diabetes in the Gran Canaria island were 5.95% (95% CI: 5.096.80%) and 5.73% (4.88-6.57%). CONCLUSIONS: Our prevalences of known and drug-treated diabetes is among the highest reported in European populations. The prescriptions of metformin and of combined therapy in DM-2, and of intensive insulin therapy in DM-1 are less frequent than expected, but nonetheless insulin therapy in DM-1 is more intensive and uses more fast-acting insulin than in DM-2.

Prevalence of obesity in a Canarian community. Association with type 2 diabetes mellitus: the Guía Study.

OBJECTIVE: We sought to estimate the prevalence of obesity and central obesity, and their association with type 2 diabetes mellitus in the Canarian community of Guía. DESIGN AND SETTING: Population-based study. SUBJECTS: A random sample of 691 subjects over 30 y old (stratified by age and sex) was studied. DATA AND MEASURES: Age, sex, family history of diabetes and medication use were obtained, height, weight and waist circumference were measured and standard oral glucose tolerance tests were performed RESULTS: The prevalences of obesity/central obesity were 36.5%/66.5% (women) and 23.6%/32.0% (men). The prevalence of diabetes was 21.0% (women) and 18.4% (men). These rank among the highest in Europe. Bivariate analyses show a strong association of both obesity and central obesity with diabetes mellitus (P<0.001), but in a multivariate model, waist circumference (P<0.001) but not body mass index (P=0.212) was retained as an independent predictor of diabetes. CONCLUSION: The prevalences of obesity, central obesity and diabetes in our community are extremely high, and central obesity is a better predictor of diabetes than obesity.

Prevalence and determinants of diabetes mellitus and glucose intolerance in a Canarian Caucasian population - comparison of the 1997 ADA and the 1985 WHO criteria. The Guía Study.

AIMS: To estimate the prevalence of diabetes mellitus, impaired fasting glucose and impaired glucose tolerance in a Canarian population according to the 1997 ADA and the 1985 WHO criteria; and to study the cardiovascular risk factors associated with these categories. METHODS: A total of 691 subjects over 30 years old were chosen in a random sampling of the population (stratified by age and sex). An oral glucose tolerance test was performed (excluding known diabetic patients) and lipids were determined in the fasting state. Anthropometric and blood pressure measurements were performed, and history of smoking habits and medications was recorded. RESULTS: The prevalence of diabetes was 15.9% (1997 ADA) and 18.7% (1985 WHO); the prevalence of impaired fasting glucose and impaired glucose tolerance was 8.8 and 17.1%, respectively. The age-adjusted prevalence of diabetes (Segi's standard world population) for the population aged 30-64 years was 12.4% (1985 WHO). The risk factors significantly associated with diabetes (1997 ADA and 1985 WHO) were age, body mass index; waist-to-hip ratio, systolic and mean blood pressure, triglycerides, total cholesterol and low HDL-cholesterol. Age, body mass index and systolic blood pressure were associated with impaired fasting glucose and impaired glucose tolerance; triglycerides were also associated with impaired fasting glucose. CONCLUSIONS: The prevalence of diabetes mellitus and glucose intolerance in Guía is one of the highest among studied Caucasian populations. The new 1997 ADA criteria estimate a lower prevalence of diabetes. Impaired fasting glucose also had a lower prevalence than impaired glucose intolerance and the overlap of these categories was modest.

["Occult" ectopic ACTH secretion syndrome: a case report]. / Síndrome de secreción ectópica de ACTH "oculto": a propósito de un caso.

The occult ectopic ACTH syndrome is ACTH-dependent hypercortisolemia of non pituitary origin, and of more than 6 months duration without the diagnosis of the origin. We report a 55 years old woman diagnosed of Cushing syndrome and treated by mean of bilateral adrenalectomy, in which is discovered an ACTH-secreting carcinoid tumor 20 years later.

[Diabetes insipidus and adipsic hypernatremia in a patient with a craniopharyngioma]. / Diabetes insípida e hipernatremia adípsica en un paciente con craneofaringioma.

A fourteen-year male patient presented a retrochiasmatic craniopharyngioma. Aer transcranial surgical resection, the patient had diabetes insipidus, which presented an interphase with manifestations of inadequate secretion of ADH. The patient was adequately treated with intranasal desmopresin, but aer i.v. fluid replacement was withdrawn, severe dehydration occurred. This was attributed to loss of the thirst reflex, due to surgical lesion of the lamina terminalis, where the osmoreceptor neurons are located. This case underscores the complications with body fluids and osmolality which may occur after surgery of hypothalamic lesions; i.e. diabetes insipidus (which may have a triphasic course), and adipsia, an infrequent complication due to absence of thirst.

[An adrenal carcinoma producing androgens, estrogens and cortisol]. / Carcinoma suprarrenal productor de andrógenos, estrógenos y cortisol.

Carcinoma of the adrenal cortex is a fairly rare entity, usually with a somber prognosis. The efficacy of treatment depends on early prognosis. We are reporting here a case of carcinoma of the adrenal cortex producing androgens, estrogens and cortisol, in which diagnosis was not achieved until two years after the onset of symptoms. Morphologic studies by CT showed local extension and metastases. After mass-reduction surgery, the patient died due to respiratory failure. This case remarks the importance of early diagnosis in this syndrome.

Prevalence of hypertension in IDDM patients in the northern Grand Canary Island, according to the WHO/ISH and JNC-V/ADA criteria.

UNLABELLED: In order to establish the prevalence of hypertension (according to both the JNC-V/ADA and the WHO/ISH criteria) in patients with insulin-dependent diabetes mellitus (IDDM), a group of 142 unselected young adults with IDDM from Northern Gran Canaria Island was cross-sectionally studied. The relationship of hypertension to diabetic nephropathy and lipid profile was also studied. Blood pressure, urinary albumin excretion and plasma lipids (total cholesterol with VLDL, LDL and HDL fractions, triglycerides and Lp(a)) were measured. The prevalence of hypertension was 11.9% (95% CI 6.5-17.3) with the WHO criteria (> 160/95 mmHg) versus 58.7% (50.5-66.9) with the JNC-V criteria (> 130/85 mmHg). The respective prevalences were 3.8 (0.0-8.1) versus 49.4% (38.0-60.7) in patients with normoalbuminuria (< or = 20 micrograms/min), 17.9 (2.7-33.0) versus 71.4% (53.6-89.3) in patients with microalbuminuria (21-200 micrograms/min), and 44.4 (9.0-69.9) versus 83.3% (64.3-100) in patients with macroalbuminuria (> 200 micrograms/min). The presence of hypertension and of micro or macroalbuminuria was associated with a worse lipid profile. IN CONCLUSION: the new JNC-V criteria drastically increase the figures of prevalence of hypertension in young insulin-dependent diabetic adults. Early and aggressive antihypertensive treatment benefits at least those patients with incipient nephropathy.