Sami T. Azar

High protein vs high carbohydrate hypoenergetic diet for the treatment of obese hyperinsulinemic subjects.

OBJECTIVE: To test the hypothesis that hyperinsulinemic obese subjects would respond differently to changes in the composition of hypoenergetic diets.DESIGN: A 4-week randomized dietary intervention trial.SUBJECTS: Thirteen male obese hyperinsulinemic normoglycemic subjects were divided into two groups and fed hypoenergetic diets providing 80% of their resting energy expenditure (REE). One group received a high-protein diet (HP; 45% protein, 25% carbohydrates, and 30% fat as percent of dietary energy) and the other a high-carbohydrate diet (HC; 12% protein, 58% carbohydrates and 30% fat).MEASUREMENTS: Anthropometry, body composition, fasting serum insulin and lipids, and REE were performed before and after the feeding period.RESULTS: Weight loss was higher in the HP than HC group (8.3±0.7 vs 6.0±0.6 kg, P<0.05). There was a decrease in body fat in both groups, whereas body water decreased significantly more in the HP group. REE decreased more in the HC than the HP group (−384.3±84.6 vs −132.3±51.0 kcal, P<0.05). Serum total cholesterol, triglycerides and LDL cholesterol decreased significantly to a similar extent in both diet groups, while HDL cholesterol was decreased significantly only in the HP group. Mean fasting insulin decreased significantly in both diet groups and reached the normal range only in the HP group.CONCLUSION: A low-carbohydrate (LC), HP hypoenergetic diet could be the diet composition of choice for a weight-reducing regimen in obese hyperinsulinemic subjects.

Variations in Postprandial Ghrelin Status following Ingestion of High-Carbohydrate, High-Fat, and High-Protein Meals in Males

Aim: The purpose of this study was to investigate the response of postprandial acylated ghrelin to changes in macronutrient composition of meals in healthy adult males. Methods: A randomized crossover study was performed. Ten healthy adult males were recruited. All subjects received, on separate occasions, a high-carbohydrate (HC), a high-fat (HF), and a high-protein (HP) meal. Blood samples were collected before and 15, 30, 60, 120, and 180 min following the ingestion of each meal. Plasma acylated ghrelin as well as serum insulin, glucose, and triglycerides were measured. Results: The levels of acylated ghrelin fell significantly following the three meals. The HC meal induced the most significant decrease in postprandial ghrelin secretion (–15.5 ± 2.53 pg/ml) as compared with HF (–8.4 ± 2.17 pg/ml) and HP (–10.0 ± 1.79 pg/ml) meals (p < 0.05). However, at 180 min, the HP meal maintained significantly lower mean ghrelin levels (29.7 ± 3.56 pg/ml) than both HC (58.4 ± 5.75 pg/ml) and HF (45.7 ± 5.89 pg/ml) meals and lower levels than baseline (43.4 ± 5.34 pg/ml) (p <0.01). The postprandial insulin levels increased to significantly higher levels following the HC meal (+80.6 ± 11.14 µU/ml) than following both HF (37.3 ± 4.82 µU/ml) and HP (51.4 ± 6.00 µU/ml) meals (p < 0.001). However, at 180 min, the mean insulin levels were found to be significantly higher following the HP meal (56.4 ± 10.80 µU/ml) as compared with both HC (30.9 ± 4.31 µU/ml) and HF (33.7 ± 4.42 µU/ml) meals (p < 0.05). Acylated ghrelin was also found to be negatively correlated with circulating insulin levels, across all meals. Conclusions: These results indicate that the nutrient composition of meals affects the extent of suppression of postprandial ghrelin levels and that partial substitution of dietary protein for carbohydrate or fat may promote longer-term postprandial ghrelin suppression and satiety. Our results also support the possible role of insulin in meal-induced ghrelin suppression.

The Link between Thyroid Function and Depression

The relation between thyroid function and depression has long been recognized. Patients with thyroid disorders are more prone to develop depressive symptoms and conversely depression may be accompanied by various subtle thyroid abnormalities. Traditionally, the most commonly documented abnormalities are elevated T4 levels, low T3, elevated rT3, a blunted TSH response to TRH, positive antithyroid antibodies, and elevated CSF TRH concentrations. In addition, thyroid hormone supplements appear to accelerate and enhance the clinical response to antidepressant drugs. However, the mechanisms underlying the interaction between thyroid function and depression remain to be further clarified. Recently, advances in biochemical, genetic, and neuroimaging fields have provided new insights into the thyroid-depression relationship.

Postprandial acylated ghrelin status following fat and protein manipulation of meals in healthy young women.

The aim of the present study was to investigate the postprandial effect of diet composition on circulating acylated ghrelin levels in healthy women. A randomized cross-over study of three experimental treatments was performed. A total of 11 healthy young women of normal body weight completed the study. All 11 subjects consumed three iso-energetic meals of different macronutrient composition, a balanced meal (50% carbohydrates, 30% fat and 20% protein), a high-fat meal (45% carbohydrates, 45% fat and 10% protein) and a high-protein meal (45% carbohydrates, 20% fat and 35% protein), for breakfast on separate days. The test meals were administered 1 month apart. Blood samples were withdrawn immediately before and at 15, 30, 60, 120 and 180 min after the test meal for measurement of plasma acylated ghrelin, as well as serum glucose, insulin and triacylglycerol (triglyceride) levels. Acylated ghrelin fell significantly after ingestion of both the balanced and high-protein meals. Ghrelin persisted at significantly lower levels than baseline for a longer duration following the high-protein meal (P<0.05 at 15, 30, 60 and 120 min) compared with the balanced meal (P<0.05 at 30 and 60 min). Moreover, acylated ghrelin levels correlated negatively with the postprandial insulin levels. In conclusion, postprandial changes in acylated plasma ghrelin depend on the macronutrient composition of the meal and are possibly influenced by insulin.

Thyroid Disorders and Diabetes Mellitus

Studies have found that diabetes and thyroid disorders tend to coexist in patients. Both conditions involve a dysfunction of the endocrine system. Thyroid disorders can have a major impact on glucose control, and untreated thyroid disorders affect the management of diabetes in patients. Consequently, a systematic approach to thyroid testing in patients with diabetes is recommended.

Biphasic insulin aspart 30 treatment improves glycaemic control in patients with type 2 diabetes in a clinical practice setting: Experience from the PRESENT study

Aim:  The Physicians’ Routine Evaluation of Safety and Efficacy of NovoMix® 30 Therapy (PRESENT) study aims to assess the safety and efficacy of biphasic insulin aspart 30 (BIAsp 30) in patients with type 2 diabetes mellitus in routine clinical practice.

The Role of Vitamin D Deficiency in the Incidence, Progression, and Complications of Type 1 Diabetes Mellitus

The “nonclassic” role of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has been recently widely recognized. In type 1 diabetes mellitus (T1D), it plays an immunomodulatory role through the vitamin D receptor (VDR) present on pancreatic and immune cells. Specific VDR allelic variants have been associated with T1D in many countries. Furthermore, vitamin D deficiency has been prevalent in T1D, and the seasonal and latitude variability in the incidence of T1D can be partly explained by the related variability in vitamin D level. In fact, retrospective studies of vitamin D supplementation during pregnancy or infancy showed a lower incidence of T1D. We will review the different mechanisms of the vitamin D protective effect against insulitis and present the available data on the role of vitamin D deficiency in the control, progression, and complications of T1D.

Homozygous familial hypercholesterolemia in Lebanon: A genotype/phenotype correlation

Familial hypercholesterolemia (FH) is an inherited disease characterized by the deposition of LDL in tissues causing premature atherosclerosis. Many genes are implicated in FH resulting in a large variability in the phenotype. DNA sequencing of the LDLR gene was done for forty patients clinically diagnosed with homozygous FH and forty family members variably affected. Patients underwent noninvasive heart and vascular studies. Statistical and pedigree analyses were used to correlate the different genotypes with the phenotypes. The prevalence of homozygosity at the Lebanese allele (2043C>A) is 45%. However, 27.5% of the patients have no mutations at all in the LDLR gene, and 27.5% are either heterozygous for the 2043C>A mutation, heterozygous for a mutation in another exon of the LDLR gene, or combined heterozygous for two different mutations. We confirm previous reports on the higher prevalence of FH in Lebanon. Our results do, however contradict previous reports on an assumed higher prevalence among the Christian Lebanese. Mutations in the LDLR especially combined heterozygosity can cause a severe phenotype similar to the homozygous mutation in the Lebanese allele. This information is particularly important in targeting the more prevalent heterozygotes in the general population with early diagnosis and intervention.

Liver disease and diabetes: Association, pathophysiology, and management

Diabetes is associated with a spectrum of liver diseases including nonalcoholic liver disease, steatohepatitis, and liver cirrhosis with their increased complications and mortality. Hepatitis C virus (HCV) and its associated liver cirrhosis has been associated with diabetes through insulin resistance. Cryptogenic diabetes occurs as a consequence of liver cirrhosis with the pathophysiology being complex, but mostly attributed to the increased insulin resistance in muscle, liver, and adipose tissue. As for the management of diabetes in patients with liver disease, lifestyle modification plays an important role. Oral diabetic medications are contraindicated in patients with advanced liver diseases with associated cirrhosis, ascites, or encephalopathy. As for stable liver disease, metformin and thiazolenediones have shown mixed results, with some showing them to be effective in improving liver transaminases in addition to histological improvement in steatosis and inflammation. α-glucosidase inhibitors may be helpful in decreasing hepatic encephalopathy. Upregulation of Dipeptidyl peptidase-4 (DPP-4) has been suggested as a possible pathogenetic mechanism for HCV-related insulin resistance, and treatment with DPP-4 inhibitors could improve insulin sensitivity in diabetic patients with liver disease. Patients with impaired liver function with associated insulin resistance may need increased insulin requirements. On the other hand patients with altered liver metabolism might need decreased insulin requirements.

Suggested insulin regimens for patients with type 1 diabetes mellitus who wish to fast during the month of Ramadan

OBJECTIVES This paper reviews available information on insulin regimens that may enable patients with type 1 diabetes mellitus to fast during the month of Ramadan with minimal complications. It also provides guidance for health care professionals in managing patients who wish to observe the fast. METHODS Relevant English-language articles were identified through searches of the MEDLINE, EMBASE, and Index Medicus Eastern Mediterranean Region databases (all, 1980-2008) conducted in February 2008 using the terms Ramadan, fasting, type 1 diabetes mellitus, hypoglycemia, and hypotension. Only original research and review articles related to adult patients with type 1 diabetes were considered for review, excluding pregnant women and patients with poorly controlled disease. RESULTS The literature review identified 5 clinical trials relevant to type 1 diabetes and fasting. Two main meals are eaten during Ramadan, one before dawn (Suhur) and the other at sunset (Iftar). Suggested adjustments to the insulin regimen during fasting include using 70% of the pre-Ramadan dose, divided as follows: 60% as insulin glargine given in the evening and 40% as an ultra-short-acting insulin (insulin aspart or lispro) given in 2 doses, 1 at Suhur and 1 at Iftar. Alternatively, 85% of the pre-Ramadan dose may be divided as 70% Ultralente and 30% regular insulin, both given in 2 doses, 1 at Suhur and 1 at Iftar. Another option is to give 100% of the pre-Ramadan morning dose of 70/330 premixed insulin at Iftar and 50% of the usual evening dose at Suhur. Patients who observe the fast should be advised to monitor their blood glucose regularly,avoid skipping meals or overeating,and maintain contact with their physician throughout the fast. The fast should be broken immediately if blood glucose drops below 60 mg/dL (3.3 mmol/L). Breaking the fast should be considered when blood glucose drops below 80 mg/dL (4.4 mmol/L), and the fast should be interrupted if blood glucose rises above 300 mg/dL (16.7 mmol/L) to avoid diabetic ketoacidosis. Fasting is contraindicated in patients with poorly controlled type 1 diabetes,including those with a history of severe hypoglycemia and/ or diabetic ketoacidosis at least 3 months before Ramadan; those with comorbid conditions (eg, unstable angina, uncontrolled hypertension, advanced macrovascular complications, infections, renal insufficiency);; those who are noncompliant with diet and medication; those who engage in intense physical activity; pregnant women; and the elderly. CONCLUSION Patients with type 1 diabetes who wish to fast during Ramadan should follow specific recommendations and be closely monitored by their physician.