BMC Endocrine Disorders - Most viewed articles

Primary prevention of diabetes mellitus type 2 and cardiovascular diseases using a cognitive behavior program aimed at lifestyle changes in people at risk: Design of a randomized controlled trial

2008-06-24

Background: The number of people with cardiovascular disease (CVD) and diabetes mellitus type 2 (T2DM) is growing rapidly. To a large extend, this increase is due to lifestyle-dependent risk factors, such as overweight, reduced physical activity, and an unhealthy diet. Changing these risk factors has the potential to postpone or prevent the development of T2DM and CVD. It is hypothesized that a cognitive behavioral program (CBP), focused in particular on motivation and self-management in persons who are at high risk for CVD and/or T2DM, will improve their lifestyle behavior and, as a result, will reduce their risk of developing T2DM and CVD. Methods: 12,000 inhabitants, 30-50 years of age living in several municipalities in the semi-rural region of West-Friesland will receive an invitation from their general practitioner (n = 13) to measure their own waist circumference with a tape measure. People with abdominal obesity (male waist ≥ 102 cm, female waist ≥ 88 cm) will be invited to participate in the second step of the screening which includes blood pressure, a blood sample and anthropometric measurements. T2DM and CVD risk scores will then be calculated according to the ARIC and the SCORE formulae, respectively. People with a score that indicates a high risk of developing T2DM and/or CVD will then be randomly assigned to the intervention group (n = 300) or the control group (n = 300).Participants in the intervention group will follow a CBP aimed at modifying their dietary behavior, physical activity, and smoking behavior. The counseling methods that will be used are motivational interviewing (MI) and problem solving treatment (PST), which focus in particular on intrinsic motivation for change and self-management of problems of the participants. The CBP will be provided by trained nurse practitioners in the participant's general practice, and will consists of a maximum of six individual sessions of 30 minutes, followed by 3-monthly booster sessions by phone. Participants in the control group will receive brochures containing health guidelines regarding physical activity and diet, and how to stop smoking. The primary outcome measures will be changes in T2DM and CVD risk scores. Secondary outcome measures will be changes in lifestyle behavior and cost-effectiveness and cost-utility ratios. All relevant direct and indirect costs will be measured, and there will be a follow-up of 24 months.DiscussionChanging behaviors is difficult, requires time, considerable effort and motivation. Combining the two counseling methods MI and PST, followed by booster sessions may result in sustained behavioral change.Trial registrationCurrent Controlled Trials ISRCTN59358434

The role of selenium, vitamin C, and zinc in benign thyroid diseases and of selenium in malignant thyroid diseases: Low selenium levels are found in subacute and silent thyroiditis and in papillary and follicular carcinoma

2008-01-25

Background: Thyroid physiology is closely related to oxidative changes. The aim of this controlled study was to evaluate the levels of nutritional anti-oxidants such as vitamin C, zinc (Zn) and selenium (Se), and to investigate any association of them with parameters of thyroid function and pathology including benign and malignant thyroid diseases. Methods: This controlled evaluation of Se included a total of 1401 subjects (1186 adults and 215 children) distributed as follows: control group (n = 687), benign thyroid disease (85 children and 465 adults); malignant thyroid disease (2 children and 79 adults). Clinical evaluation of patients with benign thyroid disease included sonography, scintigraphy, as well as the determination of fT3, fT4, TSH, thyroid antibodies levels, Se, Zn, and vitamin C. Besides the routine oncological parameters (TG, TSH, fT4, ultrasound) Se was also determined in the cases of malignant disease. The local control groups for the evaluation of Se levels were taken from a general practice (WOMED) as well as from healthy active athletes. Blood samples were collected between 8:00 and 10:30 a.m. All patients lived in Innsbruck. Statistical analysis was done using SPSS 14.0. The Ho stated that there should be no differences in the levels of antioxidants between controls and thyroid disease patients. Results: Among the thyroid disease patients neither vitamin C, nor Zn nor Se correlated with any of the following parameters: age, sex, BMI, body weight, thyroid scintigraphy, ultrasound pattern, thyroid function, or thyroid antibodies. The proportion of patients with benign thyroid diseases having analyte concentrations below external reference cut off levels were 8.7% of cases for vitamin C; 7.8% for Zn, and 20.3% for Se. Low Se levels in the control group were found in 12%. Se levels were significantly decreased in cases of sub-acute and silent thyroiditis (66.4 ± 23.1 μg/l and 59.3 ± 20.1 μg/l, respectively) as well as in follicular and papillary thyroid carcinoma. The mean Se level in the control group was 90.5 ± 20.8 μg/l. Conclusion: The H0 can be accepted for vitamin C and zinc levels whereas it has to be rejected for Se. Patients with benign or malignant thyroid diseases can present low Se levels as compared to controls. Low levels of vitamin C were found in all subgroups of patients.

Association of liver enzymes with incident type 2 diabetes: A nested case control study in an Iranian population

2008-06-05

Background: To investigate the association of Aspartate aminotransferase (AST), Alanin aminotranferase (ALT) and Gamma glutamyl transferase (GGT) with incident type 2 diabetes. Methods: In a nested case-control study, AST, ALT, GGT as well as classic diabetes risk factors, insulin and C-reactive protein (CRP) were measured in 133 non-diabetic subjects at baseline of which 68 were cases and 65 were controls. Incident diabetes was defined by the WHO 1999 criteria. Conditional logistic regression was used to calculate the odds ratio (OR) of incident diabetes associated with different hepatic markers. We used factor analysis for clustering of classic diabetes risk factors. Results: In Univariate analysis both ALT and GGT were associated with diabetes with ORs of 3.07(1.21–7.79) and 2.91(1.29–6.53) respectively. After adjustment for CRP and insulin, ALT and GGT were still predictive of incident diabetes. When the model was further adjusted for anthropometric, blood pressure and metabolic factors, only ALT was independently associated with diabetes [OR = 3.18 (1.02–9.86)]. No difference was found between the area under the receiver operating characteristic curves of the models with and without ALT (0.820 and 0.802 respectively, P = 0.4) Conclusion: ALT is associated with incident type 2 diabetes independent of classic risk factors. However, its addition to the classic risk factors does not improve the prediction of diabetes.

Validation of ICD-9-CM coding algorithm for improved identification of hypoglycemia visits

Adit A Ginde, Phillip G Blanc, Rebecca M Lieberman and Carlos A Camargo — 2008-04-01

Background: Accurate identification of hypoglycemia cases by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes will help to describe epidemiology, monitor trends, and propose interventions for this important complication in patients with diabetes. Prior hypoglycemia studies utilized incomplete search strategies and may be methodologically flawed. We sought to validate a new ICD-9-CM coding algorithm for accurate identification of hypoglycemia visits. Methods: This was a multicenter, retrospective cohort study using a structured medical record review at three academic emergency departments from July 1, 2005 to June 30, 2006. We prospectively derived a coding algorithm to identify hypoglycemia visits using ICD-9-CM codes (250.3, 250.8, 251.0, 251.1, 251.2, 270.3, 775.0, 775.6, and 962.3). We confirmed hypoglycemia cases by chart review identified by candidate ICD-9-CM codes during the study period. The case definition for hypoglycemia was documented blood glucose 3.9 mmol/l or emergency physician charted diagnosis of hypoglycemia. We evaluated individual components and calculated the positive predictive value. Results: We reviewed 636 charts identified by the candidate ICD-9-CM codes and confirmed 436 (64%) cases of hypoglycemia by chart review. Diabetes with other specified manifestations (250.8), often excluded in prior hypoglycemia analyses, identified 83% of hypoglycemia visits, and unspecified hypoglycemia (251.2) identified 13% of hypoglycemia visits. The absence of any predetermined co-diagnosis codes improved the positive predictive value of code 250.8 from 62% to 92%, while excluding only 10 (2%) true hypoglycemia visits. Although prior analyses included only the first-listed ICD-9 code, more than one-quarter of identified hypoglycemia visits were outside this primary diagnosis field. Overall, the proposed algorithm had 89% positive predictive value (95% confidence interval, 86–92) for detecting hypoglycemia visits. Conclusion: The proposed algorithm improves on prior strategies to identify hypoglycemia visits in administrative data sets and will enhance the ability to study the epidemiology and design interventions for this important complication of diabetes care.

Exercise training with dietary counselling increases mitochondrial chaperone expression in middle-aged subjects with impaired glucose tolerance

2008-03-27

Background: Insulin resistance and diabetes are associated with increased oxidative stress and impairment of cellular defence systems. Our purpose was to investigate the interaction between glucose metabolism, antioxidative capacity and heat shock protein (HSP) defence in different skeletal muscle phenotypes among middle-aged obese subjects during a long-term exercise and dietary intervention. As a sub-study of the Finnish Diabetes Prevention Study (DPS), 22 persons with impaired glucose tolerance (IGT) taking part in the intervention volunteered to give samples from the vastus lateralis muscle. Subjects were divided into two sub-groups (IGTslow and IGTfast) on the basis of their baseline myosin heavy chain profile. Glucose metabolism, oxidative stress and HSP expressions were measured before and after the 2-year intervention. Results: Exercise training, combined with dietary counselling, increased the expression of mitochondrial chaperones HSP60 and glucose-regulated protein 75 (GRP75) in the vastus lateralis muscle in the IGTslow group and that of HSP60 in the IGTfast group. In cytoplasmic chaperones HSP72 or HSP90 no changes took place. In the IGTslow group, a significant positive correlation between the increased muscle content of HSP60 and the oxygen radical absorbing capacity values and, in the IGTfast group, between the improved VO2max value and the increased protein expression of GRP75 were found. Serum uric acid concentrations decreased in both sub-groups and serum protein carbonyl concentrations decreased in the IGTfast group. Conclusion: The 2-year intervention up-regulated mitochondrial HSP expressions in middle-aged subjects with impaired glucose tolerance. These improvements, however, were not correlated directly with enhanced glucose tolerance.

Glucagon-like peptide 1 improved glycemic control in type 1 diabetes

Margaret T Behme, John Dupré and Thomas J McDonald — 2003-04-10

Background: Glucagon-like peptide-1 (GLP-1) and its agonists are under assessment in treatment of type 2 diabetes, by virtue of their antidiabetic actions, which include stimulation of insulin secretion, inhibition of glucagon release, and delay of gastric emptying. We examined the potential of GLP-1 to improve glycemic control in type 1 diabetes with no endogenous insulin secretion. Methods: Dose-finding studies were carried out to establish mid range doses for delay of gastric emptying indicated by postponement of pancreatic polypeptide responses after meals. The selected dose of 0.63 micrograms/kg GLP-1 was administered before breakfast and lunch in 8-hour studies in hospital to establish the efficacy and safety of GLP-1. In outside-hospital studies, GLP-1 or vehicle was self-administered double-blind before meals with usual insulin for five consecutive days by five males and three females with well-controlled C-peptide-negative type 1 diabetes. Capillary blood glucose values were self-monitored before meals, at 30 and 60 min after breakfast and supper, and at bedtime. Breakfast tests with GLP-1 were conducted on the day before and on the day after 5-day studies. Paired t-tests and ANOVA were used for statistical analysis. Results: In 8-hour studies time-averaged incremental (delta) areas under the curves(AUC) for plasma glucose through 8 hours were decreased by GLP-1 compared to vehicle (3.2 ± 0.9, mean ± se, vs 5.4 ± 0.8 mmol/l, p < .05), and for pancreatic polypeptide, an indicator of gastric emptying, through 30 min after meals (4.0 ± 3.1 vs 37 ± 9.6 pmol/l, p < .05) with no adverse effects. Incremental glucagon levels through 60 min after meals were depressed by GLP-1 compared to vehicle (-3.7 ± 2.5 vs 3.1 ± 1.9 ng/l, p < .04). In 5-day studies, AUC for capillary blood glucose levels were lower with GLP-1 than with vehicle (-0.64 ± 0.33 vs 0.34 ± 0.26 mmol/l, p < .05). No assisted episode of hypoglycaemia or change in insulin dosage occurred. Breakfast tests on the days immediately before and after 5-day trials showed no change in the effects of GLP-1. Conclusion: We have demonstrated that subcutaneous GLP-1 can improve glucose control in type 1 diabetes without adverse effects when self-administered before meals with usual insulin during established intensive insulin treatment programs.

Factors influencing the growth hormone peak and plasma insulin-like growth factor I in young adults with pituitary stalk interruption syndrome

Mariana Marcu, Christine Trivin, Jean-Claude Souberbielle and Raja Brauner — 2008-07-11

Background: The diagnostic criteria for growth hormone (GH) deficiency (GHD) in adolescents and young adults are not yet clearly established.We evaluated the factors influencing the GH peak and plasma insulin-like growth factor (IGF) I in order to determine the cut-off limits for the diagnosis of GHD during the transition period. Methods: 21 patients treated for GHD due to pituitary stalk interruption syndrome at 5.7 ± 4.1 years were reevaluated at 16.0 ± 1.8 years, 0.6 ± 0.6 years after the end of GH treatment. Group 1 had isolated GHD (n = 9) and group 2 had multiple pituitary deficiencies (n = 12), including deficiencies of thyroid stimulating (n = 12), adrenocorticotropin (n = 8) and gonadotropin (n = 9) hormones. Results: At diagnosis, group 1 had a greater pituitary height (2.8 ± 1.2 vs 1.6 ± 1.1 mm, P = 0.03) and GH peak (3.8 ± 1.9 vs 1.6 ± 1.5 ng/ml, P < 0.02) than did group 2.At last evaluation, group 1 had greater GH peak (3.9 ± 1.9 vs 0.2 ± 0.4 ng/ml, P = 0.0001) and plasma IGF I (211 ± 88 vs 78 ± 69 ng/ml, P < 0.002) than did group 2. No group 1 and 9 group 2 patients had an undetectable GH peak, while the 3 others had GH peak below 1 ng/ml.The GH peak decreased between diagnosis and last evaluation only in group 2 (P < 0.008). Conclusion: The GH peak response to pharmacological stimulation and the plasma IGF I concentration in young adults with GHD of childhood onset depend on the presence of additional pituitary deficiencies, reflecting a more severe defect of the hypothalamic-pituitary axis. The sex steroids cannot increase the IGF I if the GH secretion is zero.

Diagnostic accuracy of basal TSH determinations based on the intravenous TRH stimulation test: An evaluation of 2570 tests and comparison with the literature

Helga Moncayo, Otto Dapunt and Roy Moncayo — 2007-08-02

Background: Basal TSH levels reflect the metabolic status of thyroid function, however the definition and interpretation of the basal levels of TSH is a matter of controversial debate. The aim of this study was to evaluate basal TSH levels in relation to the physiological response to i.v. TRH stimulation. Methods: A series of 2570 women attending a specialized endocrine unit were evaluated. A standardized i.v. TRH stimulation test was carried out by applying 200 μg of TRH. TSH levels were measured both in the basal and the 30 minute blood sample. The normal response to TRH stimulation had been previously determined to be an absolute value lying between 2.5 and 20 mIU/l. Both TSH values were analyzed by cross tabulation. In addition the results were compared to reference values taken from the literature. Results: Basal TSH values were within the normal range (0.3 to 3.5 mIU/l) in 91,5% of cases, diminished in 3,8% and elevated in 4.7%. Based on the response to TRH, 82.4% were considered euthyroid, 3.3% were latent hyperthyroid, and 14.3% were latent hypothyroid. Combining the data on basal and stimulated TSH levels, latent hypothyroidism was found in the following proportions for different TSH levels: 5.4% for TSH < 2.0 mIU/l, 30.2% for TSH between 2.0 and 3.0 mIU/l, 65,5% for TSH between 3.0 and 3.50 mIU/l, 87.5% for TSH between 3.5 and 4.0 mIU/l, and 88.2% for TSH between 4 and 5 mIU/l. The use of an upper normal range for TSH of 2.5 mIU/l, as recommended in the literature, misclassified 7.7% of euthyroid cases. Conclusion: Our analysis strategy allows us to delineate the predictive value of basal TSH levels in relation to latent hypothyroidism. A grey area can be identified for values between 3.0 and 3.5 mIU/l.

Study Protocol: insulin and its role in cancer

K Harish, M Dharmalingam and M Himanshu — 2007-10-22

Background: Studies have shown that metabolic syndrome and its consequent biochemical derangements in the various phases of diabetes may contribute to carcinogenesis. A part of this carcinogenic effect could be attributed to hyperinsulinism. High levels of insulin decrease the production of IGF-1 binding proteins and hence increase levels of free IGF-1. It is well established that bioactivity of free insulin growth factor 1 (IGF-1) increases tumor turnover rate. The objective is to investigate the role of insulin resistance/sensitivity in carcinogenesis by studying the relation between insulin resistance/sensitivity and IGF-1 levels in cancer patients. We postulate that hyperinsulinaemia which prevails during initial phases of insulin resistance (condition prior to overt diabetes) increases bioactivity of free IGF-1, which may contribute to process of carcinogenesis.Methods/DesignBased on our pilot study results and power analysis of the same, we have designed a two group case-control study. 800 proven untreated cancer patients (solid epithelial cell tumors) under age of 50 shall be recruited with 200 healthy subjects serving as controls. Insulin resistance/sensitivity and free IGF-1 levels shall be determined in all subjects. Association between the two parameters shall be tested using suitable statistical methods.DiscussionWell controlled studies in humans are essential to study the link between insulin resistance, hyperinsulinaemia, IGF-1 and carcinogenesis. This study could provide insights to the role of insulin, insulin resistance, IGF-1 in carcinogenesis although a precise role and the extent of influence cannot be determined. In future, cancer prevention and treatment strategies could revolve around insulin and insulin resistance.

Diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome after renal transplantation in the United States

Kevin C Abbott, Victor J Bernet, Lawrence Y Agodoa and Christina M Yuan — 2003-03-24

Background: The incidence and risk factors for diabetic ketoacidosis (diabetic ketoacidosis) and hyperglycemic hyperosmolar syndrome (hyperglycemic hyperosmolar syndrome, previously called non-ketotic hyperosmolar coma) have not been reported in a national population of renal transplant (renal transplantation) recipients. Methods: We performed a historical cohort study of 39,628 renal transplantation recipients in the United States Renal Data System between 1 July 1994 and 30 June 1998, followed until 31 Dec 1999. Outcomes were hospitalizations for a primary diagnosis of diabetic ketoacidosis (ICD-9 code 250.1x) and hyperglycemic hyperosmolar syndrome (code 250.2x). Cox Regression analysis was used to calculate adjusted hazard ratios for time to hospitalization for diabetic ketoacidosis or hyperglycemic hyperosmolar syndrome. Results: The incidence of diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome were 33.2/1000 person years (PY) and 2.7/1000 PY respectively for recipients with a prior diagnosis of diabetes mellitus (DM), and 2.0/1000 PY and 1.1/1000 PY in patients without DM. In Cox Regression analysis, African Americans (AHR, 2.71, 95 %CI, 1.96–3.75), females, recipients of cadaver kidneys, patients age 33–44 (vs. >55), more recent year of transplant, and patients with maintenance TAC (tacrolimus, vs. cyclosporine) had significantly higher risk of diabetic ketoacidosis. However, the rate of diabetic ketoacidosis decreased more over time in TAC users than overall. Risk factors for hyperglycemic hyperosmolar syndrome were similar except for the significance of positive recipient hepatitis C serology and non-significance of female gender. Both diabetic ketoacidosis (AHR, 2.44, 95% CI, 2.10–2.85, p < 0.0001) and hyperglycemic hyperosmolar syndrome (AHR 1.87, 95% CI, 1.22–2.88, p = 0.004) were independently associated with increased mortality. Conclusions: We conclude that diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome were associated with increased risk of mortality and were not uncommon after renal transplantation. High-risk groups were identified.