Kegg Pathway: Type II diabetes mellitus

Exp Clin Endocrinol diabetes. 2009 Nov; 117(10): 573-576
Ozbek M, Erdogan M, Karadeniz M, Cetinkalp S, Ozgen AG, Saygili F, Yilmaz C, Tuzun M

BACKGROUND AND AIMS: Defective insulin secretion is required for the development of frank diabetes mellitus. We evaluated the secretory response of pancreatic beta cells after the ingestion of mixed meal plus oral L-arginine in newly diagnosed Type 2 diabetic patients. MATERIALS AND METHODS: Twenty-four newly diagnosed Type 2 diabetic patients were enrolled in this study. All patients were ingested a mixed meal of 553 kcal. Serum insulin levels were measured at time 0 just before the mixed meal and at 1, 2, 3, 4 and 5 h after the ingestion of the mixed meal. Twenty-four hours later, all patients ingested mixed meal followed by oral 8 g L-Arginine, and insulin levels were again measured at 0, 1, 2, 3, 4 and 5 h after the ingestion of the meal. RESULTS: Insulin levels reached to peak values at the 2 (nd) hour, and decreased to baseline levels at the 5 (th) hour measurements both after the ingestion of mixed meal only and after the ingestion of mixed meal plus oral L-Arginine. First and 2 (nd) hour insulin levels were significantly higher after the ingestion of mixed meal plus oral L-Arginine. CONCLUSION: In this study we used for the first time the combination of oral L-arginine with mixed meal test to evaluate the beta cell dysfunction in Type 2 diabetic patients. Increments regarding serum insulin levels after the ingestion of mixed meal plus oral L-Arginine suggest that oral L-Arginine could be benefical for the evaluation of beta cell function and secretory defects.

PLoS One. 2009; 4(11): e7697
Sousa AG, Marquezine GF, Lemos PA, Martinez E, Lopes N, Hueb WA, Krieger JE, Pereira AC

BACKGROUND: TCF7L2 polymorphisms have been consistently associated with Type 2 diabetes mellitus in different populations and Type 2 diabetes mellitus is a major risk factor for cardiovascular disease, especially coronary artery disease. This study aimed to evaluate the association between TCF7L2 polymorphism rs7903146 and coronary artery disease in diabetic and non-diabetic subjects. METHODS AND RESULTS: two populations were studied in order to assess severity of coronary artery disease and cardiovascular events incidence. Eight-hundred and eighty nine subjects who were referred for cardiac catheterization for coronary artery disease diagnosis were cross-sectionally evaluated for coronary lesions (atherosclerotic burden) and 559 subjects from the MASS-II Trial were prospectively followed-up for 5 years and assessed for major cardiovascular events incidence. As expected, rs7903146 T allele was associated with diabetes. Although diabetic patients had a higher prevalence of coronary lesions, no association between TCF7L2 genoType and coronary lesions was found in this subgroup. However, non-diabetic individuals carrying the T allele were associated with a significantly higher frequency of coronary lesions than non-diabetic non-carriers of the risk allele (adjusted OR = 2.32 95%CI 1.27-4.24, p = 0.006). Moreover, presence of multi-vessel coronary artery disease was also associated with the CT or TT genoTypes in non-diabetics. Similarly, from the prospective sample analysis, non-diabetics carrying the CT/TT genoTypes had significantly more composite cardiovascular end-points events than CC carriers (p = 0.049), mainly due to an increased incidence of death (p = 0.004). CONCLUSIONS: rs7903146 T allele is associated with diabetes and, in non-diabetic individuals, with a higher prevalence and severity of coronary artery disease and cardiovascular events. name of registry site (see list below), registration number, trial registration URL in brackets. CLINICAL TRIAL REGISTRATION INFORMATION: MEDICINE, ANGIOPLASTY, OR SURGERY STUDY (MASS II): Unique identifier: ISRCTN66068876.

Nat Rev Endocrinol. 2009 Dec; 5(12): 682-693
Prudente S, Morini E, Trischitta V

Type 2 diabetes mellitus (T2DM) is a complex disorder that has a heterogeneous genetic and environmental background. In this Review, we discuss the role of relatively infrequent polymorphisms of genes that regulate insulin signaling (including the K121Q polymorphism of ENPP1, the G972R polymorphism of IRS1 and the Q84R polymorphism of TRIB3) in T2DM and other conditions related to insulin resistance. The biological relevance of these three polymorphisms has been very thoroughly characterized both in vitro and in vivo and the available data indicate that they all affect insulin signaling and action as well as insulin secretion. They also affect insulin-mediated regulation of endothelial cell function. In addition, several reports indicate that the effects of all three polymorphisms on the risk of T2DM and cardiovascular diseases related to insulin resistance depend on the clinical features of the individual, including their body weight and age at disease onset. Thus, these polymorphisms might be used to demonstrate how difficult it is to ascertain the contribution of relatively infrequent genetic variants with heterogeneous effects on disease susceptibility. Unraveling the role of such variants might be facilitated by improving disease definition and focusing on specific subsets of patients.

Orv Hetil. 2009 Nov 1; 150(48): 2173-2181
Hagymási K, Reismann P, Rácz K, Tulassay Z

The most frequent liver disorder in metabolic syndrome is the nonalcoholic fatty liver disease. Its pathogenesis is a complex, multifactorial process, characterized by insulin resistance and involvement of the endocrine system. Hypothyroidism may lead to nonalcoholic steatohepatitis via hyperlipidemia and obesity. Adult patients with growth hormone deficiency have a metabolic syndrome-like phenoType with obesity and many characteristic metabolic alterations. The chronic activation of the hypothalamic-pituitary-adrenal axis results in metabolic syndrome as well. Cushing's syndrome has also features of metabolic syndrome. Mild elevation of transaminase activities is commonly seen in patients with adrenal failure. Non-alcoholic steatosis is twice as common in postmenopusal as in premenopausal women and hormonal replacement therapy decreases the risk of steatosis. Insulin resistance, diabetes mellitus Type 2, sleeping apnoe syndrome, cardiovascular disorders and non-alcoholic fatty liver disease are more frequent in polycystic ovary syndrome. Hypoandrogenism in males and hyperandrogenism in females may lead to fatty liver via obesity and insulin resistance. Adipokines (leptin, acylation stimulating protein, adiponectin) have a potential role in the pathogenesis of nonalcoholic fatty liver. The alterations of endocrine system must be considered in the background of cryptogenic liver diseases. The endocrine perspective may help the therapeutic approaches in the future.

Neurobiol Aging. 2009 Nov 16;
Sato T, Hanyu H, Hirao K, Kanetaka H, Sakurai H, Iwamoto T

To test the effects of the PPAR-gamma agonist pioglitazone on cognition, regional cerebral blood flow (rCBF), and plasma levels of Abeta40 and Abeta42, we conducted a 6-month, randomized, open-controlled trial in patients with mild Alzheimer disease (AD) accompanied with Type II diabetes mellitus. We randomly assigned 42 patients to either the group treated with 15-30mg pioglitazone daily (n=21, pioglitazone group) or not (n=21, control group). The pioglitazone group improved cognition and rCBF in the parietal lobe, while the control group showed no such improvement. The plasma Abeta40/Abeta42 ratio increased in the control group, but showed no significant change in the pioglitazone group. Both groups showed good control of diabetes during the study. In addition, pioglitazone treatment resulted in a decrease in fasting plasma insulin levels, indicating enhanced insulin sensitivity. The results of this pilot study demonstrated that pioglitazone exhibited cognitive and functional improvements, and stabilization of the disease in diabetic patients with AD. Pioglitazone may offer a novel strategy for the treatment of AD.

Metabolism. 2009 Nov 17;
Annuzzi G, Bozzetto L, Patti L, Santangelo C, Giacco R, Di Marino L, De Natale C, Masella R, Riccardi G, Rivellese AA

We investigated postprandial plasma and adipose tissue (AT) adiponectin changes in relation to obesity and Type 2 diabetes mellitus. Fasting and 6 hours after a standard fat-rich meal blood samples (adiponectin, glucose, insulin, lipids) and needle biopsies of abdominal subcutaneous AT (adiponectin messenger RNA, lipoprotein lipase activity) were taken in 10 obese diabetic (OD), 11 obese nondiabetic (OND), and 11 normal-weight control (C) men. The OD and OND subjects had similar adiposity (body mass index, waist circumference) and insulin resistance (hyperinsulinemic euglycemic clamp). Fasting plasma adiponectin and AT gene expression were not significantly different between groups. After meal, plasma adiponectin decreased in OD but significantly increased in OND and C, the changes being significantly different between groups (analysis of variance, P = .01); adiponectin messenger RNA decreased in OD (-0.27 +/- 0.25 AU, P = .01) but was unchanged in OND (P = .59) and C (P = .45). After meal, plasma adiponectin correlated inversely with triglyceride and cholesterol concentrations in chylomicrons and large very low-density lipoprotein, and directly with AT lipoprotein lipase activity (P < .05 for all). Type 2 diabetes mellitus is associated with lower postprandial plasma levels and AT gene expression of adiponectin independently of degree of adiposity and whole-body insulin sensitivity. In patients with diabetes, this may exacerbate postprandial abnormalities of lipoprotein metabolism.

Metabolism. 2009 Nov 17;
Nabipour I, Kalantarhormozi M, Larijani B, Assadi M, Sanjdideh Z

Osteoprotegerin (OPG) is an inhibitor of bone resorption. Circulating levels of OPG seem to be elevated in patients with cardiovascular disorders and diabetes. The relationship between OPG and the metabolic syndrome has never been studied in postmenopausal women. In a population-based study, 382 Iranian postmenopausal women were randomly selected. Cardiovascular risk factors, high-sensitivity C-reactive protein, and OPG were measured. The diabetes classification and the metabolic syndrome definition were based on the criteria of the American diabetes Association and the National Cholesterol Education Program-Adult Treatment Panel III, respectively. The mean serum OPG level was higher in those with Type 2 diabetes mellitus than those without diabetes (4.33 +/- 1.70 vs 3.84 +/- 1.76 pmol/L, P = .016). In multiple logistic regression analysis, Type 2 diabetes mellitus showed a significant association with serum OPG levels when adjustments were made for age, high-sensitivity C-reactive protein, and cardiovascular risk factors (odds ratio = 2.21; confidence interval, 1.34-3.66; P = .002). No significant difference was found between the mean serum OPG levels of those with the metabolic syndrome and those without the metabolic syndrome. Mean OPG levels did not differ significantly between subjects with and without hypertension, dyslipidemia, glucose intolerance, or abdominal obesity according to the National Cholesterol Education Program-Adult Treatment Panel III criteria. In conclusion, circulating OPG levels are significantly associated with diabetes, independent of cardiovascular risk factors in postmenopausal women. However, OPG levels have no correlation with the metabolic syndrome or its components. Further studies are warranted to determine the pathophysiologic origin of elevated OPG in Type 2 diabetes mellitus.

Metabolism. 2009 Nov 17;
Kadoglou NP, Iliadis F, Sailer N, Athanasiadou Z, Vitta I, Kapelouzou A, Karayannacos PE, Liapis CD, Alevizos M, Angelopoulou N, Vrabas IS

The aim of the study was to investigate the effects of rosiglitazone and/or exercise training on novel cardiovascular risk factors in patients with Type 2 diabetes mellitus. One hundred overweight/obese Type 2 diabetes mellitus patients, with inadequate glycemic control (hemoglobin A(1c) >7%) despite combined treatment with gliclazide plus metformin, were randomized using a 2 x 2 factorial design to 4 equivalent (n = 25) groups, as follows: (1) CO: maintenance of habitual activities, (2) RSG: add-on therapy with rosiglitazone (8 mg/d), (3) EX: adjunctive exercise training, and (4) RSG + EX: supplementary administration of rosiglitazone (8 mg/d) plus exercise training. No participant had diabetic vascular complications or was receiving lipid-lowering therapy. Anthropometric parameters, cardiorespiratory capacity, glycemic and lipid profile, apolipoprotein (apo) A-I, apo B, interleukin (IL)-10, IL-18, insulin resistance, and blood pressure were measured before and after 12 months of intervention (P < .05). Both RSG and EX groups significantly reduced glycemic indexes, insulin resistance, blood pressure, and IL-18, whereas they significantly increased high-density lipoprotein, cardiorespiratory capacity, and IL-10, compared with CO group (P < .05). Besides this, exercise-treated patients conferred a remarkable down-regulation in the rest of lipid parameters (total cholesterol, low-density lipoprotein cholesterol, triglycerides, apo B) and body fat content (P < .05) in comparison with CO group. On the other hand, RSG group rather than CO group considerably increased apo A-I levels and body mass index (P < .05). Notably, the combined treatment group yielded pronounced beneficial changes in glycemic indexes, lipid profile, insulin resistance, blood pressure, IL-10, IL-18, apo A-I, and apo B (vs CO group, P < .05). Furthermore, the addition of exercise to rosiglitazone treatment counteracted the drug-related negative effects on body weight, low-density lipoprotein, and total cholesterol. Rosiglitazone plus exercise training elicited additive effects on body composition, glycemic control, and traditional and novel cardiovascular risk factors in Type 2 diabetes mellitus patients, indicating complementary effects.

Clin Sci (Lond). 2009; 118(5): 341-349
Newsholme P, Homem De Bittencourt PI, O' Hagan C, De Vito G, Murphy C, Krause MS

It is now widely accepted that hypertension and endothelial dysfunction are associated with an insulin-resistant state and thus with the development of T2DM (Type 2 diabetes mellitus). Insulin signalling is impaired in target cells and tissues, indicating that common molecular signals are involved. The free radical NO* regulates cell metabolism, insulin signalling and secretion, vascular tone, neurotransmission and immune system function. NO* synthesis is essential for vasodilation, the maintenance of blood pressure and glucose uptake and, thus, if levels of NO* are decreased, insulin resistance and hypertension will result. Decreased blood levels of insulin, increased AngII (angiotensin II), hyperhomocysteinaemia, increased ADMA (asymmetric omega-NG,NG-dimethylarginine) and low plasma L-arginine are all conditions likely to decrease NO* production and which are associated with diabetes and cardiovascular disease. We suggest in the present article that the widely reported beneficial effects of exercise in the improvement of metabolic and cardiovascular health are mediated by enhancing the flux of muscle- and kidney-derived amino acids to pancreatic and vascular endothelial cells aiding the intracellular production of NO*, therefore resulting in normalization of insulin secretion, vascular tone and insulin sensitivity. Exercise may also have an impact on AngII and ADMA signalling and the production of pro- and anti-inflammatory cytokines in muscle, so reducing the progression and development of vascular disease and diabetes. NO* synthesis will be increased during exercise in the vascular endothelial cells so promoting blood flow. We suggest that exercise may promote improvements in health due to positive metabolic and cytokine-mediated effects.

J Altern Complement Med. 2009 Nov; 15(11): 1215-1221
Dwivedi S, Aggarwal A

Abstract Background: India is currently facing the silent epidemic of ischemic heart disease, Type 2 diabetes mellitus (T2DM), hypertension, and stroke. Both diabetes and ischemic heart disease appear in Indian people a decade earlier compared to whites. The recent evidence that certain medicinal plants possess hypoglycemic, lipid-lowering, and immunomodulating properties on account of their rich flavonoid and/or other glucose-lowering active constituents merits scientific scrutiny in this regard. Objectives: The present communication aims to give a brief review of those plants that could be useful in T2DM associated with hypertension, ischemic heart disease, and/or dyslipidemia. Methods: Aegle marmelos (bael), Allium sativum (garlic), Curcuma domestica (turmeric), Eugenia jambolana (jamun), Murraya koenigII (curry leaves), Trigonella foenum graecum (fenugreek), and Terminalia arjuna (arjun) have been found to be useful in diabetes associated with ischemic heart disease. Their active biomolecules have been identified. They have also been demonstrated to be safe in long-term use. Conclusions: Further clinical research regarding their potency and efficacy vis-à-vis oral hypoglycemics needs to done.

Zhonghua Wei Chang Wai Ke Za Zhi. 2009 Nov; 12(6): 554-557
Hu XG, Zheng CZ, Ji XR, Zhou DL, Chen DL, Yin K, Ke CW

OBJECTIVE: To evaluate the short-term outcome of laparoscopic gastric bypass on obesity patients with Type 2 diabetes mellitus. METHODS: Seven obesity patients with Type 2 diabetes mellitus received laparoscopic gastric bypass(n=1) or laparoscopic minigastric bypass(n=6), and their data of treatment outcomes were analyzed. RESULTS: The operations were all successfully performed without any complications. The average operation time was 125 minutes(range:100 to 170 minutes). The patients underwent 1-18 months follow-up after operation. Diabetic indicators returned to normal without any medication and body weight reduced by on average of 24.3 kg. CONCLUSION: Laparoscopic gastric bypass and minigastric bypass have good short-term outcome in the treatment of obesity patients with Type 2 diabetes mellitus.

Adv Ther. 2009 Nov 16;
Stein LL, Dong MH, Loomba R

Nonalcoholic fatty liver disease (NAFLD), first described in 1980, is now recognized as one of the most common causes of elevated liver enzymes and chronic liver disease in Western countries. The incidence of NAFLD in both adults and children is rising, in conjunction with the burgeoning epidemics of obesity and Type 2 diabetes mellitus. NAFLD often coexists with other sequelae of the metabolic syndrome: central obesity, Type 2 diabetes, hypertension, and hyperlipidemia. NAFLD encompasses a spectrum of pathologic liver diseases ranging from simple hepatic steatosis to a predominant lobular necro-inflammation, with or without centrilobular fibrosis (called nonalcoholic steatohepatitis or NASH). NASH can progress to cirrhosis, decompensated liver disease, and hepatocellular carcinoma. Though the natural history of NASH is still not clearly defined, it has been observed to progress to cirrhosis in 15%-220% of those affected. Insulin resistance is nearly universal in NASH and is thought to play an important role in its pathogenesis leading to dysregulated lipid metabolism. The prevalence of insulin resistance is reported in the general population to be approaching 45%, suggesting that NAFLD and NASH will contin nue to be an important public health concern. To date, NASH has proven to be a difficult disease to treat. Front-line therapy with lifestyle modifications resulting in weight loss through decreased caloric intake and moderate exercise is generally believed to be beneficial in patients with NASH, but is often difficult to maintain long term. Given that insulin resistance plays a dominant role in the pathogenesis, many studies have examined the use of insulin sensitizers: the biguanides (metformin), thiazolidinediones (pioglitazone, troglitazone, and rosiglitazone), glucagon-like peptide-1-receptor agonists, or incretins (exenatide)in NASH. This review will provide an overview of insulin resistance in NAFLD and provide a detailed summary on the clinical data regarding the use of insulin sensitizers in NASH.

Drug Des Devel Ther. 2009; 3: 219-240
Robles GI, Singh-Franco D

BACKGROUND: Incretin glucagon-like peptide-1 (GLP-1) is a hormone released from cells in the gastrointestinal tract (GI), leading to glucose-dependent insulin release from the pancreas. It also suppresses postprandial hyperglycemia, glucagon secretion and slows gastric emptying. Exenatide (EXE), a functional analog of human GLP-1, was approved by the US FDA in April 2005. OBJECTIVE: This article reviews current primary literature on the clinical efficacy and safety of EXE in the treatment of Type 2 diabetes mellitus (DM) and describes the pharmacokinetics, pharmacodynamics, dosing and administration of EXE. METHODS: English-language articles were identified through a search of MEDLINE (1966 to March 2009), International Pharmaceutical Abstracts (1970 to present), and Cochrane Database of Systemic Reviews (1995 to March 2009). Search terms included EXE, diabetes mellitus, postprandial hyperglycemia, gastric emptying, glucagon, pharmacokinetics and pharmacodynamics. Articles were selected for review if their designs were randomized, blinded and of controlled design that focused on clinical outcomes of patients with Type 2 DM. RESULTS: EXE is administered subcutaneously in the thigh, abdomen or upper arm within the 60-minute period before the morning and evening meals. Its C(max) is reached within 2.1 hours, and its T(1/2) in 2.4 hours. EXE's metabolism is primarily through the kidneys. For the patients who received EXE 10 mug SC BID in three, 30-week, placebo-controlled studies with background sulfonylureas (SUs), metformin (MET), or SU + MET, there were significant reductions in HbA(1c) (0.77 to 0.86%), fasting plasma glucose (0.6 mmol/L) and body weight (1.6 to 2.8 kg) (P 20%) reported in patients receiving the highest dose of EXE (10 mug SC BID vs 5 mug SC BID). CONCLUSIONS: EXE at the dose of 10 mug SC BID has been proven to decrease HbA(lc) by 1.3% +/- 0.1% and decrease body weight by up to 5.3 +/- 0.8 kg at week 82. Nausea was the most frequently reported adverse event (>20%) especially in patients being treated with EXE 10 mug SC BID. EXE can be safely added to MET therapy, SU therapy or MET + SU combination to effectively target glycemic goals in patients with Type 2 DM. Long-term, head-to-head studies assessing the effect of the EXE +/- oral agents/insulins in patients with HbA(lc) >/= 10% are still needed to fully clarify the role of EXE in poorly controlled patients with Type 2 DM.

Circulation. 2009 Nov 17;
Hlatky MA, Boothroyd DB, Melsop KA, Kennedy L, Rihal C, Rogers WJ, Venkitachalam L, Brooks MM,

BACKGROUND: -The economic outcomes of clinical management strategies are important in assessing their value to patients. Methods and Results-Bypass Angioplasty Revascularization Investigation 2 diabetes (BARI 2D) randomized patients with Type 2 diabetes mellitus and angiographically documented, stable coronary disease to strategies of (1) prompt revascularization versus medical therapy with delayed revascularization as needed to relieve symptoms and (2) insulin sensitization versus insulin provision. Before randomization, the physician declared whether coronary artery bypass grafting or percutaneous coronary intervention would be used if the patient were assigned to revascularization. We followed 2005 patients for medical utilization and costs and assessed the cost-effectiveness of these management strategies. Medical costs were higher for revascularization than medical therapy, with a significant interaction with the intended method of revascularization (P<0.0001). In the coronary artery bypass grafting stratum, 4-year costs were $80 900 for revascularization versus $60 600 for medical therapy (P<0.0001). In the percutaneous coronary intervention stratum, costs were $73 400 for revascularization versus $67 800 for medical therapy (P<0.02). Costs also were higher for insulin sensitization ($71 300) versus insulin provision ($70 200). Other factors that significantly (P<0.05) and independently increased cost included insulin use and dose at baseline, female sex, white race, body mass index >/=30, and albuminuria. Cost-effectiveness based on 4-year data favored the strategy of medical therapy over prompt revascularization and the strategy of insulin provision over insulin sensitization. Lifetime projections of cost-effectiveness showed that medical therapy was cost-effective compared with revascularization in the percutaneous coronary intervention stratum ($600 per life-year added) with high confidence. Lifetime projections suggest that revascularization may be cost-effective in the coronary artery bypass grafting stratum ($47 000 per life-year added) but with lower confidence. Conclusions-Prompt coronary revascularization significantly increases costs among patients with Type 2 diabetes mellitus and stable coronary disease. The strategy of medical therapy (with delayed revascularization as needed) appears to be cost-effective compared with the strategy of prompt coronary revascularization among patients identified a priori as suitable for percutaneous coronary intervention. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00006305.

Circulation. 2009 Nov 17;
Chaitman BR, Hardison RM, Adler D, Gebhart S, Grogan M, Ocampo S, Sopko G, Ramires JA, Schneider D, Frye RL,

BACKGROUND: -The Bypass Angioplasty Revascularization Investigation 2 diabetes (BARI 2D) trial in 2368 patients with stable ischemic heart disease assigned before randomization to percutaneous coronary intervention or coronary artery bypass grafting strata reported similar 5-year all-cause mortality rates with insulin sensitization versus insulin provision therapy and with a strategy of prompt initial coronary revascularization and intensive medical therapy or intensive medical therapy alone with revascularization reserved for clinical indication(s). In this report, we examine the predefined secondary end points of cardiac death and myocardial infarction (MI). Methods and Results-Outcome data were analyzed by intention to treat; the Kaplan-Meier method was used to assess 5-year event rates. Nominal P values are presented. During an average 5.3-year follow-up, there were 316 deaths (43% were attributed to cardiac causes) and 279 first MI events. Five-year cardiac mortality did not differ between revascularization plus intensive medical therapy (5.9%) and intensive medical therapy alone groups (5.7%; P=0.38) or between insulin sensitization (5.7%) and insulin provision therapy (6%; P=0.76). In the coronary artery bypass grafting stratum (n=763), MI events were significantly less frequent in revascularization plus intensive medical therapy versus intensive medical therapy alone groups (10.0% versus 17.6%; P=0.003), and the composite end points of all-cause death or MI (21.1% versus 29.2%; P=0.010) and cardiac death or MI (P=0.03) were also less frequent. Reduction in MI (P=0.001) and cardiac death/MI (P=0.002) was significant only in the insulin sensitization group. Conclusions-In many patients with Type 2 diabetes mellitus and stable ischemic coronary disease in whom angina symptoms are controlled, similar to those enrolled in the percutaneous coronary intervention stratum, intensive medical therapy alone should be the first-line strategy. In patients with more extensive coronary disease, similar to those enrolled in the coronary artery bypass grafting stratum, prompt coronary artery bypass grafting, in the absence of contraindications, intensive medical therapy, and an insulin sensitization strategy appears to be a preferred therapeutic strategy to reduce the incidence of MI. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00006305.

Blood Press. 2009 Oct 29; 18(5): 247-254
Pascual JM, Rodilla E, Costa JA, Perez-Lahiguera F, Gonzalez C, Lurbe E, Redón J

Abstract Objective. The objective was to assess the impact of weight changes on blood pressure (BP), lipids and glucose goals in a cohort of hypertensive subjects. Design. Prospective follow-up. Setting. Hypertension clinic. Patients. 326 hypertensive non-diabetic subjects, 46% with metabolic syndrome (MS). Interventions. Usual care treatment, which included diet, physical exercise and drugs prescribed when indicated. All patients were observed for up to 1 year. Main outcome measures. BP and low-density lipoprotein-cholesterol (LDL-C) goal were those in ESH/ESC and ATP III recommendations, respectively. The glucose goal was to delay progression to Type 2 diabetes mellitus, or to achieve blood glucose <100mg/dl for non-diabetics. According to body weight changes, patients were categorized using adjusted ROC curves models. Results. Overall, there was a significant weight increment of 0.5kg (95% CI 0.1-0.9kg); 28 patients (8.6%) lost more than 5kg, and only four (1.2%) lost more than 10kg. BP, LDL-C and glucose goals were achieved in 56%, 78% and 61% of patients, respectively. To lose or not gain weight was an independent prognostic factor to achieve the BP goal in all the patients and the LDL goal in the presence of MS. For glucose control, being treated with beta-blockers and/or diuretics was a negative factor. Conclusions. In hypertensive subjects, even small changes in weight may have an important impact on achieving cardiovascular goals, mainly in those with MS.

Curr Med Res Opin. 2009 Nov 18;
Tunis SL, Minshall ME

Abstract Objective: Stakeholders in the US and elsewhere are interested in country-specific and cohort-specific information with which to assess the long-term value of self-monitoring of blood glucose (SMBG) for patients with Type 2 diabetes mellitus (T2DM) on oral anti-diabetes drugs (OADs). This study modeled the cost-effectiveness of SMBG at frequencies of once, twice, or three times per day for this population, and included those who had used SMBG in the prior year. Research design and methods: Based on clinical findings of a longitudinal Kaiser Permanente study, a validated model was used to project 40-year clinical and economic outcomes for SMBG at (averages of) once, twice, or three times per day versus no SMBG. Baseline HbA1c (7.6%), age and gender represented the Kaiser study 'prevalent' SMBG users cohort. Unit costs came primarily from a 2003 published article; inflated to US$2006. Outcomes were discounted at 3% per annum, with sensitivity analyses on discount rates and time horizons. Analyses were conducted from a third-party payer perspective in the US, including only direct costs. Main outcome measures: Primary outcomes were differences in total costs, cumulative incidence of complications, quality-adjusted life years (QALYs); and incremental cost-effectiveness ratios (ICERs). Results: For patients using SMBG once, twice, or three times per day, relative risks over 40 years were lower for 14 of 16 complications and slightly higher for 2 complications. Compared to 'no SMBG,' QALYs increased with SMBG frequency: 0.047, 0.116, and 0.132 QALYs for SMBG once, twice, and three times per day, respectively. Some increased costs with SMBG were offset by reductions in costs for several diabetes-related complications. Corresponding ICERs were $26 206, $18 572 and $25 436/QALY gained. Results were most sensitive to time horizon, with SMBG not cost-effective over a 5-year simulation period. Conclusions: Study limitations include the use of relatively short-term observational data, unknown levels of patient adherence, and assumptions regarding the duration of clinical effects. Results showed that compared to no SMBG, base case ICERs for each of the three SMBG frequencies examined were below $30 000, and that a portion of the increased costs associated with SMBG were offset by reductions in complication costs, and by modest increases in QALYs. Results add to the literature addressing the cost-effectiveness of SMBG as a component of care for T2DM patients on OADs, and in particular those with monitoring experience within the previous year.

G Ital Nefrol. 2009 Nov-Dec; 26(6): 679-85
Libardi F, Sirolli V, Cappelli P, Bonomini M

Type 2 diabetes mellitus is one of the most common disease worldwide. diabetes mellitus is expected to affect over 380 million people by 2025 and one third of these patients will develop chronic kidney disease (CKD). There are many categories of hypoglycemic agents available for treatment of Type 2 diabetes mellitus: sulphounilureas, glinides, biguanides, thiazolidinediones, alpha-glucosidase inhibitors, and the new brand incretines. In nephropatic patients with CKD stage I-II, any hypoglycemic agent can be used: the choice must be linked to a careful evaluation of potential risk and benefit. In CKD stage III to V, conversely, some drugs are not recommended while other agents can be used with dose reduction due to risk of hypoglycemia. In these patients the early use of insulin may be indicated. The target of this review is to evaluate evidences about the possible use of hypoglycemic agents in patients affected by diabetes and CKD stage III-V.

Cases J. 2009; 2: 6792
Helal I, Goucha R, Karoui C, Abderrahim E, Hamida FB, Elyounsi F, Maiz HB, Abdallah TB, Kheder A

INTRODUCTION: Diabetic nephropathy can occur during the course of both Type1 and Type 2 diabetes mellitus. The characteristic lesions are diffuse or nodular (Kimmelsteil-Wilson) diabetic glomerulosclerosis. The reported cases represent unusual presentations of diabetes mellitus. CASE PRESENTATION: We report the case of a 49-year-old man without prior history of diabetes mellitus who presented with rapidly progressive renal failure and whose renal biopsy revealed nodular (Kimmelsteil-Wilson) glomerulosclerosis lesions characteristic of diabetes. CONCLUSION: Renal manifestations of diabetes mellitus may antedate other more common presenting symptoms of this disease and we critically review the literature on this subject.

Cases J. 2009; 2: 6988
Chiang E, Packer CD

Warm antibody autoimmune hemolytic anemia is due to the presence of warm agglutinins that react with protein antigens on the surface of red blood cells causing premature destruction of circulating red blood cells. We report the first case of concurrent reactive arthritis, Graves' disease, and autoimmune hemolytic anemia. A 40-year-old man with reactive arthritis, Graves' disease, Type 2 diabetes mellitus, mitral valve prolapse, and Gilbert's disease presented with a one month history of jaundice, fatigue, and black stools. After diagnosis of warm autoimmune hemolytic anemia, the patient was started on prednisone 1 mg/kg with rapid improvement in his anemia and jaundice. Our subject's mother and possibly his maternal grandmother also had autoimmune hemolytic anemia, which raises the possibility of hereditary autoimmune hemolytic anemia, a rarely reported condition.