Israel Medical Association Journal

Objectives: To assess the prevalence of metabolic syndrome and different glucose intolerance states in healthy, overweight Arab individuals attending a primary healthcare clinic in Israel.

Methods: We randomly recruited 95 subjects attending a primary healthcare clinic who were healthy, overweight (body mass index >27) and above the age of 40. Medical and family history was obtained and anthropometric parameters measured. Blood chemistry and oral glucose tolerance test were performed after overnight fasting.

Results: Twenty-seven percent of the subjects tested had undiagnosed type 2 diabetes according to WHO criteria, 42% had impaired fasting glucose and/or impaired glucose tolerance and only 31% had a normal OGTT[1]. Metabolic syndrome was found in 48% according to criteria of the U.S. National Cholesterol Education Program, with direct correlation of this condition with BMI[2] and insulin resistance calculated by homeostasis model assessment. Subjects with metabolic syndrome had a higher risk for abnormality in glucose metabolism, and the more metabolic syndrome components the subject had the higher was the risk for abnormal glucose metabolism. Metabolic syndrome predicted the result of OGTT with 0.67 sensitivity and 0.78 specificity. When combined with IFG[3], sensitivity was 0.83 and specificity 0.86 for predicting the OGTT result.

Conclusions: According to our initial evaluation approximately 70% of the overweight Arab population in Israel has either metabolic syndrome or abnormal glucose metabolism, indicating that they are at high risk to develop type 2 diabetes and cardiovascular morbidity and mortality. This population is likely to benefit from an intervention program.

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[1] OGTT = oral glucose tolerance test

[2] BMI = body mass index

[3] IFG = impaired fasting glucose
 

Background: Repaglinide, a new insulin secretagogue, is purported to be as effective as sulphonylurea but is less hypoglycemic-prone.

Objectives: To assess the efficacy of repaglinide and its proclivity for hypoglycemia in a post-marketing study.

Methods: The study group comprised 688 patients, aged 26–95 years, clinically diagnosed with non-insulin-dependent type 2 diabetes. The patients were divided into three groups based on previous therapy: a) sulphonylurea-treated (group 1, n=132); b) metformin with or without sulphonylurea where sulphonylurea was replaced with repaglinide. (group 2, n=302); and c) lifestyle modification alone (drug-naïve) (group 3, n=254). At initiation of the study, all patients were transferred from their current treatment to repaglinide. Only patients in group 2, with combined sulphonylurea plus metformin, continued with metformin plus repaglinide. Fasting blood sugar, hemoglobin A1c and weight were measured at study entry and 4–8 weeks following repaglinide therapy. A questionnaire documented the number of meals daily and the presence of eating from fear of hypoglycemia.

Results: The fasting blood sugar level of the entire cohort dropped from 191 ± 2.4 to 155 ± 2.0 mg/dl (P < 0.0001); HbA1c from 8.8 ± 0.1 to 7.7 ± 0.1% (P < 0.0001). The drop of HbA1c in groups 1, 2 and 3 respectively were: 1.04 ± 0.22% (P < 0.0001), 1.14 ± 0.24% (P < 0.0001), and 1.51 ± 0.31% (P = 0.0137). Weight dropped from 81 ± 0.7 to 80.2 ± 0.7 kg (P < 0.0001), and eating from fear of hypoglycemia from 157 to 97 (P < 0.001). The daily number of meals decreased from 2.9 ± 0.4 to 2.4 ± 0.4 (P < 0.001). No serious adverse reactions occurred during the study.

Conclusions: Repaglinide is an effective oral hypoglycemic agent taken either as monotherapy or combination therapy. There is less eating to avoid hypoglycemia, fewer meals consumed, and weight loss.

Background: Repaglinide, a new insulin secretagogue, is purported to be as effective as sulphonylurea but is less hypoglycemic-prone.

Objectives: To assess the efficacy of repaglinide and its proclivity for hypoglycemia in a post-marketing study.

Methods: The study group comprised 688 patients, aged 26–95 years, clinically diagnosed with non-insulin-dependent type 2 diabetes. The patients were divided into three groups based on previous therapy: a) sulphonylurea-treated (group 1, n=132); b) metformin with or without sulphonylurea where sulphonylurea was replaced with repaglinide. (group 2, n=302); and c) lifestyle modification alone (drug-naïve) (group 3, n=254). At initiation of the study, all patients were transferred from their current treatment to repaglinide. Only patients in group 2, with combined sulphonylurea plus metformin, continued with metformin plus repaglinide. Fasting blood sugar, hemoglobin A1c and weight were measured at study entry and 4–8 weeks following repaglinide therapy. A questionnaire documented the number of meals daily and the presence of eating from fear of hypoglycemia.

Results: The fasting blood sugar level of the entire cohort dropped from 191 ± 2.4 to 155 ± 2.0 mg/dl (P < 0.0001); HbA1c from 8.8 ± 0.1 to 7.7 ± 0.1% (P < 0.0001). The drop of HbA1c in groups 1, 2 and 3 respectively were: 1.04 ± 0.22% (P < 0.0001), 1.14 ± 0.24% (P < 0.0001), and 1.51 ± 0.31% (P = 0.0137). Weight dropped from 81 ± 0.7 to 80.2 ± 0.7 kg (P < 0.0001), and eating from fear of hypoglycemia from 157 to 97 (P < 0.001). The daily number of meals decreased from 2.9 ± 0.4 to 2.4 ± 0.4 (P < 0.001). No serious adverse reactions occurred during the study.

Conclusions: Repaglinide is an effective oral hypoglycemic agent taken either as monotherapy or combination therapy. There is less eating to avoid hypoglycemia, fewer meals consumed, and weight loss.
 

The prevalence of obesity worldwide has risen sharply during the last four decades. The etiology of obesity is complex and includes a host of genetic influences in addition to the overconsumption of energy coupled with a sedentary lifestyle. Obesity is known to cause or exacerbate many co-morbid conditions such as diabetes, hypertension, dyslipidemia, coronary heart disease, stroke, certain cancers, arthritis and obstructive sleep apnea. Modest weight losses of 5–10% of actual weight are related to significant improvements in co-morbid conditions, but unfortunately the rate of recidivism with short-term therapy for obesity is high. The recent recognition of obesity as a chronic disease that should be treated with long-term programs and possibly with polypharmacy, and the alarming increase in its prevalence, have prompted extensive research and the development of new pharmacotherapy.

Since both major forms of diabetes involve inadequate function of pancreatic beta cells, intensive research is ongoing to better understand how beta cells perform their complex role of secreting the hormone insulin in response to physiologic needs. Identification and characterization of pancreatic transcription factors has revealed that they play a crucial role not only in maintenance of mature beta-cell function but also at multiple stages in pancreatic development. Furthermore, recent reports have revealed their potential to convert non-beta cells into insulin-producing cells, which in some cases can function to ameliorate diabetes in experimental animals. The ability to translate these successes to the clinic will require a detailed mechanistic understanding of the molecular basis of action of these proteins. Specific gene regulation in beta cells involves the action of multiple transcription factors recruited to the promoter and functioning synergistically to activate transcription, in part through recruitment of co-activator proteins and components of the basal transcriptional machinery. In addition, the process involves modification of chromatin structure, the details of which are beginning to be elucidated. Our ability to modulate gene expression patterns may lead to developing ways to provide an unlimited supply of functional beta cells for transplantation, permitting a dramatic improvement in therapeutic options for diabetes.

Type 1 diabetes mellitus is caused by an autoimmune destruction of pancreatic islet beta cells, leading to insulin deficiency. Beta-cell replacement is considered the optimal treatment for type 1 diabetes, however it is severely limited by the shortage of human organ donors. An effective cell replacement strategy depends on the development of an abundant supply of beta cells and their protection from recurring immune destruction. Stem/progenitor cells, which can be expanded in tissue culture and induced to differentiate into multiple cell types, represent an attractive source for generation of cells with beta-cell properties: insulin biosynthesis, storage, and regulated secretion in response to physiologic signals. Embryonic stem cells have been shown to spontaneously differentiate into insulin-producing cells at a low frequency, and this capacity could be further enhanced by tissue culture conditions, soluble agents, and expression of dominant transcription factor genes. Progenitor cells from fetal and adult tissues, such as liver and bone marrow, have also been shown capable of differentiation towards the beta-cell phenotype in vivo, or following expression of dominant transcription factors in vitro. These approaches offer novel ways for generation of cells for transplantation into patients with type 1 diabetes.

Background: The management of diabetes in preschool children poses unique difficulties for both the families and the medical team.

Objective: To test the feasibility and safety of insulin pump therapy in the 1–6 year age group in order to improve quality of life and metabolic control.

Methods: The study group comprised 15 type 1 diabetic children aged 1–6 years old (mean ± SD, 3.8 ± 1.2 years) from three diabetes centers. Insulin pump therapy was applied for 12 months. Data, including insulin dose, hemoglobin A1c, hypoglycemic events, as well as scores on the Diabetes Quality of Life Measure Questionnaire and the Diabetes Treatment Satisfaction Questionnaire, were collected and compared with the multiple daily injections treatment prior to entry into the study.

Results: HbA1c[1] was measured at the beginning of the study and at 2, 4, 8 and 12 months later; the respective levels (mean ± SD) were 8.82 ± 0.98, 8.45 ± 1.05, 8.37 ± 0.85, 8.32 ± 0.71, 8.18 ± 0.90%. HbA1c measurements after 12 months were significantly lower than at the beginning of the study (P < 0.05). There were no significant differences in insulin dose and the total number of hypoglycemic events. In both the DQOL[2] and DTSQ[3] scales there were significant differences in scores in favor of the insulin pump period (43.7 ± 8.0 versus 33.7 ± 7.9, P < 0.001; and 10.9 ± 2.3 versus 14.5 ± 2.3, P < 0.001), respectively.

Conclusions: For very young diabetic children, insulin pump therapy improves quality of life and is feasible and safe. It should be considered as an optional mode of therapy for this age group.