Clinical Medicine: Endocrinology and Diabetes: Gender-associated Differences in Weight Gain, Insulin Requirement and Metabolic control in Newly Insulin-treated Type 2 Diabetic Patients with Secondary Sulfonylurea Failure–-a One-year Observation

Objective The aim of the present study was to determine differences between male and female type 2 diabetic patients concerning body weight, metabolic control, insulin requirement and prevalence of vascular diseases during the first year insulin therapy. Patients and Methods We investigated 102 newly insulin-treated type 2 diabetic patients (60 female) with secondary sulfonylurea failure. Observation period was the first year insulin therapy. We compared BMI, HbA1c, lipids and insulin requirement at the begin and after one year, C-peptide and prevalence of vascular diseases at the start of insulin therapy. Results At the start of insulin substitution, omen had a higher BMI (27 + 3 versus 25 + 3; p < 0.05). Women also required a higher insulin dose than did men (28 + 6 versus 24 + 6 IU/day) Mean HbA1c and cholesterol levels were similar in both groups whereas triglycerides were higher in women (244 + 88 versus 203 + 76 mg/dl; p < 0.05). Both groups achieved a similar gain in body weight after one year (+2.5% versus +2.6%; NS). HbA1c decreased from 9.2 + 1.1 to 7.4% + 0.9% (–19%) in women and from 9.4 + 1.1 to 7.5% + 1.0% (–20%) in men. The prevalence of vascular diseases was not significantly different in both groups. Conclusions At the start of insulin therapy female type 2 diabetic patients showed a significant higher BMI and a higher insulin requirement than male patients. The metabolic control was similar in men and women, only the triglycerides were higher in the female patients. Weight gain and increase of needed insulin as well as prevalence of macroangiopathy were the same in both groups.

Racial Disparities on Glycemic Control and Lipid Profiles in Children with Type 1 Diabetes

Objective We assessed the racial (Black–White) differences in glycemic control, prevalence of abnormal lipid profiles and factors influencing temporal trends in children with type 1 diabetes (T1DM). Methods This retrospective study was done in children with T1DM. The outcome measure was based on glycemic control and all lipid determinations which were stratified according to the published guidelines. Results The study included 181 children; 76.2% Whites and 23.8% Blacks. The mean glycated hemoglobin (A1C) was higher in Blacks than in Whites (p < 0.0001). Blacks had elevated total cholesterol (TC) (p = 0.0013), lower TC/HDL ratio (p < 0.0001) and higher concentration of HDL (<0.0001) when compared to Whites. The longitudinal analyses over a 5 year period showed changes in A1C significantly associated with changes in the lipid profiles. The lipid profiles in Blacks were more altered by the trend in A1C with changes in the TC (p = 0.0079), non-HDL (p < 0.0001) and HDL (p < 0.0001). Conclusions Black children with T1DM have poorer glycemic control. However they retained excellent levels of HDL when compared to Whites.

Chronic Complications of Diabetes in Iraq: Experience from Southern Iraq

Background The aim of this study is to evaluate the prevalence of chronic complications in type 2 diabetic patients in Basrah (Southern Iraq). Methods This was a longitudinal descriptive study for patients with diabetes registered in Al-Faiha Diabetes and Endocrine Centre in Basrah (Southern Iraq) for the period from April 2003 to end of February 2009. Results Out of 4,926 patients enrolled, 51.0% were women, mean age was 55.0 ± 13.1 years and 67.6% were overweight or obese. Those with duration of diabetes more than 5 years constituted 50.6% and only 25.3% were on insulin. Mean Hemoglobin A1C was 9.3 ± 2.0. The prevalence of the 16 complications studied were as follows: Hypertension in 31.0%, peripheral neuropathy in 13.8%, ischemic heart disease in 7.8%, proteinuria in 6.6%, cereberovascular accident in 4.6%, interdigital fungal infection in 4.3%, heart failure in 3.4%, and erectile dysfunction in 6.0%. In this study 2.8% of patients died of cardiovascular causes, 2.7% developed diabetic foot, 2.4% had non-alcoholic fatty liver, 0.7% had amputation, 0.4% developed ophthalmoplegia, 0.2% had peripheral vascular disease, and 0.04% developed mucormycosis. The chronic complications which were more seen in those with diabetes more than 5 years were hypertension, peripheral neuropathy, ischemic heart disease, proteinuria, cereberovascular accident, heart failure, erectile dysfunction, cardiovascular death, diabetic foot, amputation and peripheral vascular disease. Conclusion This study provided the baseline for chronic complications of diabetes in Iraq. Screening for early complications is recommended.

Intestinal Obstruction and Pheochromocytoma in a Patient Suffering from von Recklinghausen's Disease

GISTs are rare neoplasms, which were recently identified to be a distinct pathologic entity. They can develop in patients with neurofibromatosis type 1 (NF1) or may be sporadic. NF1 is one of the most common inherited diseases and is a complex disease, with patients having an increased prevalence of benign and malignant tumors, including pheochromocytomas. The association of pheochromocytoma(s) and GISTs in NF1 is very rare. We report an additional case of this triple association in a normotensive 60-year-old female with NF1 admitted for intestinal obstruction: a pheochromocytoma of the left adrenal gland was discovered and surgical resection is performed. We provide an overview of the literature. The coexistence of NF1-related pheochromocytoma and GISTs is uncommon, but perhaps not fortuitous, and endocrinologists should be aware of this.

Article Commentary: Clinical Medicine: Endocrinology and Diabetes: Insulin Resistance–-a Link between Inflammation and Hepatocarcinogenesis?

The incidence of hepatocellular carcinoma (HCC) is increasing world wide. The risk factors for the development of HCC include liver cirrhosis, chronic alcohol intake, and chronic viral hepatitis. These conditions are associated with inflammation, liver cell injury, and oxidative stress. The signaling pathways that contribute to liver cell injury have been shown to also promote insulin resistance in hepatocytes. On the other hand, obesity and diabetes have been suggested as risk factors for the development of chronic liver disease and HCC. The molecular mediators (e.g. stress kinases) and signaling pathways that contribute to cellular injury, proliferation and insulin resistance are also activated in chronic liver disease. At this time it is still unknown whether (1) IR will help to identify patients that are of increased risk for progressive liver disease or (2) if improving IR will be beneficial to patients with chronic liver disease. Future research will have to expand our knowledge on mediators of inflammation and liver cell injury within clinical trials to establish whether IR should be included in every hepatologists work up as a cofactor for chronic liver disease.

Insulin Resistance and Hyperinsulinemia in Patients with Chronic Liver Disease and Hepatocellular Carcinoma

Objectives To investigate the role of insulin resistance (IR) and insulin plasma levels (IRI) in patients with chronic liver disease (CLD) and hepatocellular carcinoma (HCC). Methods We recruited the following patients: 125 with HCC, 128 with liver cirrhosis (LC) and 133 with chronic hepatitis C (CHC). IR was assessed by the HOMA-IR method. To define IR and hyperinsulinemia we selected as a cut-off level, the value of the 80th percentile for HOMA-IR (2.72) and IRI (11.18) in 113 healthy subjects. Results The mean levels of HOMA-IR and IRI increase progressively among CHC (2.7 ± 2.9 and 11.5 ± 10.5, respectively), LC (5.4 ± 4.5 and 17.6 ± 11.2) and HCC (6.4 ± 9.8 and 18.2 ± 18.8). In the upper quintiles for HOMA-IR and IRI, the frequency of patients in the LC and HCC groups was twice as much in CHC cases. HCC with DM2 have the greatest percentage above the 80th percentile of HOMA-IR, their quintiles distribution is inverted and HOMA-IR mean values are significantly higher in comparison with HCC without DM2 cases. Discussion Our study shows that the association between IR and CLD begins in the early stages of liver fibrosis. DM2 increases HOMA-IR and IRI mean levels in HCC patients and these metabolic factors could play a major role in the link between diabetes mellitus and hepatocarcinoma.

The Impact of Obesity on Adverse Cardiovascular Outcomes in the General Population and in patients with Type 2 Diabetes

Objectives There is an established causal link between obesity and cardiovascular outcomes. The aim of this review was to determine whether an independent relationship exists between anthropometric measurements of weight (typically body mass index [BMI]) and cardiovascular outcomes (e.g. angina, myocardial infarction, congestive heart failure, stroke, and mortality due to cardiovascular disease) in the general population and in patients with type 2 diabetes. Methods A review of the medical literature published between 1988 and May 2008 was conducted using the PubMed, EMBASE, Cochrane and Center for Review and Dissemination databases. Studies longer than 12 months, with ≥500 adult subjects and published in English were included. Results In studies conducted in general populations there was an overall trend towards increased risk for adverse cardiovascular outcomes with increasing BMI. The nature and strength of this relationship varied according to the measurement used (e.g. BMI, waist circumference, waist-to-hip ratio) and the population studied, with notable differences observed in Asian/Asia-Pacific compared with European or North American-based studies. However, data from diabetes-specific populations are limited. Conclusions In general, the degree of being overweight or obese was associated with an elevated risk of adverse cardiovascular events and mortality. Although inextricable links exist between obesity, type 2 diabetes and cardiovascular disease in the general population, the extent to which findings can be extrapolated to a diabetes-specific population is limited.

Article Commentary: Insulin Resistance, Type 2 Diabetes and Chronic Liver Disease. A Deadly Trio

In this commentary to the paper by Donadon V. et al (Clinical Medicine: Endocrinology and Diabetes. 2009;2:25–33.) the association and significance of insulin resistance with chronic liver disease are shortly reviewed and the molecular mechanisms underlying the diabetogenic and oncogenic potentials of advanced liver disease are summarized. Literature studies demonstrate that hepatocellular carcinoma (HCC) can be part of the natural history of NASH. HCCs in patients with features of metabolic syndrome as the only risk factor for liver disease have distinct morphological characteristics and mainly occur in the absence of significant fibrosis in the background liver. Moreover, data indicate that the presence of diabetes carries an approximately three to four-fold increased risk of HCC and such a risk is strongly increased by concurrent viral infections. Finally, the relationship between insulin resistance, steatosis and diabetes in NAFLD and HCV infection will be commented, along with the directions for future studies.

Clinical Medicine: Endocrinology and Diabetes: Abnormality of Serum Lipids are Independently Associated with Increased Serum Calcium Level in the Adult Newfoundland Population

Some epidemiological evidence shows a link between abnormality of lipid profiles and variations in serum calcium. However, it is unknown whether this association resulted from confounding factors. The present study was designed to investigate the relationship between serum lipids and calcium. Serum calcium was corrected for albumin. Major confounding factors including age, gender, medications, menopause, parathyroid hormone (PTH) and 25-OH-vitamin D status were controlled in analyses. A total of 1907 adult subjects from the province of Newfoundland and Labrador (NL), Canada participated in the study. Significant positive correlations were detected between serum total cholesterol and high density lipoprotein-cholesterol (HDL-c) with variations of serum Ca++ in both genders (p < 0.05–0.0001). Significant positive correlations were additionally detected between triglycerides (TG) and low density lipoprotein-cholesterol (LDL-c) with Ca++ in women only (p < 0.0001) in partial correlation analyses. Similar significant results were detected in both females and males not taking any medication. Analyses were performed based on menopausal status as well. Significant correlations were seen in both pre- and post-menopausal women but higher correlation coefficients were observed in pre-menopausal women as compared to post-menopausal women. Subjects with low calcium levels had the lowest concentration of total cholesterol, TG, HDL-c and LDL-c, while subjects with high calcium levels had the highest concentration of all four markers in women. The significant associations between cholesterol, TG and LDL-c and serum Ca++ remained after calcium was adjusted for 25-OH-vitamin D and PTH. Our results indicate that the abnormality of serum lipid profiles are significantly correlated with altered serum Ca++ levels independent of age, obesity status, medication, phosphorus, magnesium, 25-OH-vitamin D and PTH.

The Impact of Planned Visits on Patients with Type 2 Diabetes Mellitus

Objectives To investigate whether planned visits improve glycemic, blood pressure and lipid control among patients with type 2 diabetes mellitus (DM). Methods The study was conducted from July 2007 to February 2008 at a primary care clinic in Rancho Cordova, California. One hundred eighty-three patients were invited to come to a planned visit. On the day of the visit, they were provided a copy of their most recent test results and information on American Diabetes Association recommendations for A1C, lipid, and blood pressure control. Afterwards, they met with their physician for a 15-minute focused appointment. Finally, they met with a diabetic nurse educator. There was no subsequent contact with the nurse educator after the planned visit. We compared the baseline measurements to those from a follow-up visit with the primary care provider at a follow-up over a 6 month period. The comparison group in this study were those who did not accept the invitation for a planned visit. Their outcomes were monitored over the same time horizon. Results One hundred eighty-three patients attended one of a total of five planned visit sessions. There were 212 patients in the comparison group. There were no significant differences for the measured baseline characteristics. There were significant improvements in A1C, LDL-C, and diastolic blood pressure control in the planned visit group. The mean A1C change was –0.61% (95% confidence interval, –0.28, –0.70); P < 0.001). The mean LDL-C change was -8.8 mg/dL (95% confidence interval, –12.2, 6.1); P < 0.05. The mean diastolic blood pressure change was -2.0 mmHg (95% confidence interval, –4.7, 6.7); P < 0.05. Patients who participated in a planned visit also reported a significantly higher frequency of self-care behaviors and greater understanding about diabetes care. Discussion Planned visits led to improvements in glycemic, lipid and blood pressure control over a 6 month observation period. Patients attending planned visits also reported improvements in self-care behaviors and a greater understanding about diabetes care.