Israel Medical Association Journal

This review summarizes the clinical, metabolic and genetic characteristics of early-onset type 2 diabetes in Mexico. Early-onset type 2 diabetes is both a clinical challenge and a public health problem. It is calculated that almost 300,000 Mexican diabetics are diagnosed between the ages of 20 and 40. The large Mexican family structure and the high prevalence of the disease provide a unique opportunity to identify the genes and the metabolic abnormalities involved in this form of the disease. In a hospital-based population, our group found that insulin deficiency was the main defect in this form of diabetes. Mutations in the HNF-1α or HNF-4α genes or autoimmunity to the beta cell were found in a small proportion of cases, leaving unexplained the majority of cases. Also discussed are the epidemiologic and therapeutic implications of early-onset type 2 diabetes, and the possible role of genetic testing for prevention.

Recent data have shed significant new light on the structural and functional development of the kidneys, as well as on a rare congenital form of bilateral renal hypoplasia called congenital oligomeganephronia. In this renal disorder, few greatly enlarged and hard-working nephrons are found that will ultimately sclerose and lead to end-stage renal failure during early childhood. At the same time it has been recognized that the number of nephrons in the kidneys of various animal species and humans is correlated to renal mass. Therefore, premature babies and/or infants small for gestational age due to intrauterine malnutrition will be born with relatively small kidneys and a certain nephron deficit, a condition called congenital oligonephropathy. Extensive worldwide epidemiologic studies have now shown that these premature or SGA[1] infants have a high incidence of cardiovascular disease, hypertension, hyperlipidemia, diabetes and renal failure in adulthood. Although the pathophysiologic mechanisms responsible for these complications of premature birth are not entirely understood, it has become clear that the described association may pose a possible health problem in the adult population. This review describes the background of COMN[2] and CON[3] as well as the evidence that has accumulated on the adult complications of the latter. In addition, some thoughts are presented on the importance of identifying subjects possibly affected by CON, such that early recognition may alter the ultimate outcome.

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Background: Pregnant diabetic women are often subjected to frequent and prolonged hospitalizations to assure tight glycemic control, but in recent years attempts have been made at ambulatory control. The financial and social advantages of ambulatory management are obvious, but no report to date has prospectively compared its efficacy with that of hospitalization.

Objectives: To evaluate the efficacy and cost of ambulatory care as compared to repeated hospitalizations for management of diabetes in pregnancy.

Methods: We conducted an 8 year prospective controlled study that included 681 diabetic women, experiencing 801 singleton pregnancies, with commencement of therapy prior to 34 gestational weeks. During 1986–1989, 394 pregnancies (60 pre-gestational diabetes mellitus and 334 gestational diabetes mellitus) were managed by hospitalization, and for the period 1990–1993, 407 pregnancies (61 PGDM and 346 GDM) were managed ambulatorily. Glycemic control, maternal complications, perinatal mortality, neonatal morbidity and hospital cost were analyzed.

Results: There was no difference in metabolic control and pregnancy outcome in women with PGDM between the hospitalized and the ambulatory groups. Patients with GDM who were managed ambulatorily had significantly lower mean capillary glucose levels, later delivery and higher gestational age at induction of labor as compared to their hospitalized counterparts. In this group there were also lower rates of neonatal hyperbilirubinemia, phototherapy and intensive care unit admissions and stay. The saved hospital cost (in Israeli prices) in the ambulatory group was $6,000 and $15,000 per GDM and PGDM pregnancy, respectively.

Conclusions: Ambulatory care is as effective as hospitalization among PGDM patients and more effective among GDM patients with regard to glycemic control and neonatal morbidity. This is not only more convenient for the pregnant diabetic patient, but significantly reduces treatment costs.
 

Background: Knowledge of the prevalence of chronic disease in the population is essential for health planners and providers.

Objectives:To present the results of a concentrated effort by the largest health maintenance organization in Israel (Clalit Health Services) in order to develop a comprehensive register of chronic diseases.

Methods: In 1998, all 2,704 primary care physicians in Israel’s largest health provider were requested to report on all patients with selected chronic diseases. In addition, all the filled prescriptions for medications relevant to the investigated diseases and all relevant hospitalization events were added to the database. Prevalence rates were calculated based on the reporting practices only (1,653 physicians responsible for a total of 1,409,725 adults).

Results: Hypertension (10.2/100), diabetes (6.1/100), hyperlipidemia (5.7/100), peptic ulcer (4.7/100) and ischemic heart disease (4.3/100) were the most prevalent. Females had significantly higher rates of hypothyroidism, psychoses, neu­roses and malignancies, and lower rates of ischemic heart disease, chronic obstructive pulmonary disease, heart failure and asthma. Arabs had higher rates of diabetes mellitus and lower rates of ischemic heart disease, hypertension and hyperlipidemia than Jews. About 20% of the adult population had one or more of the selected chronic diseases.

Conclusions: Differences in rates noted between physi­cians, not explainable by population characteristics, may reflect differences in the quality and delivery of health services. Rate differences between demographic subgroups call for further studies on the etiology, susceptibility and natural history of these diseases.
 

Trophic factors such as nerve and fibroblast growth factors are important modulators of 13 cell physiology. These two factors induce the extension of neurite-Iike processes in primary cultures of adult rat 13 cells. Moreover, both NGF and FGF enhance glucose-induced insulin secretion. Since â cells synthesize NGF and pancreatic islet cells produce FGFs, it is possible that autocrine/paracrine interactions may be major regulators of insulin secretion, and impairment of these interactions could lead to pathological states such as diabetes mellitus.

Background: Information is lacking on the effects of hormone replacement therapy in women with diabetes, especially during moderate chronic hyperglycemia.

Objectives: To study the effects of HRT on the lipid profile and the low density lipoprotein subclass distribution in women with type 2 diabetes under satisfactory and non-satisfactory glycemic control.

Methods: Fifty-four postmenopausal women after a 6 week run-in diet were randomized to receive either placebo(HbAlc <8%, n=13 HbAlc >8%, n=17) or HRT (HbAlc<8%, n=11 HbAlc >8%, n=13) for 12 weeks. HRT consisted of cyclical conjugated estrogens 0.625 mg/day plus medrogestone 5 mg/day. At the beginning and at the end of each treatment period the LDL subclass distribution was estimated by density gradient ultracentrifugation.

Results: At the baseline and during the study, the HbAlc level was significantly higher in hyperglycemic patients than in the near-normoglycemic controls (baseline 10.2±2.9 vs. 6.5±0.7%, P<0.01). They showed a trend for higher total and LDL cholesterol, triglycerides and lower high density lipoprotein-cholesterol compared to near-normoglycemic con­trols, as well as significantly higher triglyceride concentrations in very low density lipoprotein, intermediate density lipoprotein and LDL-1 particles and cholesterol content in LDL-1 and -2 particles. HRT decreased LDL-cholesterol in both groups. In the normoglycemic patients a small increase in HbAlc was observed (6.5±0.7 vs. 7.4+1%, P=004). In all cases, HRT did not modify the proportion of LDL represented by denser LDLs.

Conclusions: HRT did not modify the LDL subclass distribution, even in the presence of moderate chronic hyperglycemia in women with type 2 diabetes.

Background: Diabetes mellitus is a serious, costly and growing public health problem. Very few studies have been published on the economic impact of diabetes in Israel.

Objective: To estimate health fund expenditures and rates of hospitalization for general conditions among the diabetic population in Israel.

Methods: The total number of hospitalization. All hospitals in Israel were included.

Results: There were 618,317 general admissions for a total of 3,005,288 hospitalization days. Analysis by age revealed that diabetic patients over age 45 represented 18.3% of all admissions and 17.5% of all hospitalization days. The average stay in hospital expenditure of the GSF for general medical conditions among diabetic patients in 1998 was estimated at US $173,455,790, of which 57% accounted for the daily hospitalization cost. Of the total hospital expenditures for that year, 13.3% was allocated to patients with diabetes of whom 96.4% were over 45 years old.

No significant difference was found between males and females.

Conclusion: Hospital expenditures for diabetic people increase with patient age and represent one-fifth of the total health insurance expenditure for the middle-aged and elderly population.

Background: In simultaneous pancreas-kidney transplantation, with both organs coming from the same donor, the addition of a pancreas to the kidney transplant does not jeopardize the kidney allograft outcome despite higher postoperative SPK morbidity. Pancreas allograft outcome has recently improved due to better organ selection and more accurate surgical techniques.

Objective: To demonstrate the positive impact of SPK on kidney allograft outcome versus kidney transplantation alone in insulin-dependent diabetes mellitus patients with end-stage renal failure.

Methods: We performed 39 consecutive SPKs in 14 female and 25 male IDDM patients with renal failure after an average waiting time of 9 months. Multi-organ donor age was 30 years (range 12-53). The kidneys were transplanted in the left retroperitoneal iliac fossa following completion of the pancreas transplantation; kidney cold ischemia time was 16±4 hours. Induction anti-rejection therapy was achieved with polyclonal antithymocytic globulin and methylprednisolone, and maintenance immunosuppression by triple drug therapy (prednisone, cyclosporine or tacrolimus, and azathioprine or mycophenolate mofetil). Infection and rejection were closely monitored.

Results: All kidney allografts produced immediate urinary output following SPK. Two renal grafts had mild function impairment due to acute tubular damage but recovered after a short delay. Three patients died from myocardial infarction, cerebrovascular event and abdominal sepsis on days 1, 32 and 45 respectively (1 year patient survival 92%). An additional kidney allograft was lost due to a renal artery pseudo-aneurysm requiring nephrectomy on day 26. Nineteen patients (49%) had an early rejection of the kidney that was resistant to pulse-steroid therapy in 6. No kidney graft was lost due to rejection. Patients with acute kidney-pancreas rejection episodes suffered from severe infection, which was the main cause of morbidity with a 55% re-admission rate. Complications of the pancreas allograft included graft pancreatitis and sepsis, leading to a poor kidney outcome with sub-optimal kidney function at 1 year. Kidney graft survival at one year was 89% or 95% after censoring the data for patients who died with functioning grafts.

Conclusions: Eligible IDDM patients with advanced diabetic nephropathy should choose SPK over kidney transplantation alone from either a cadaver or a living source.

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SPK= simutaneous pancreas-kidney transplatation

IDDM= insulin-dependent diabetes mellitus

Background: The pattern of diabetes and ischemic heart disease among emigrants from pre-industrialized societies to more developed countries may be explained by both genetic and environmental factors.

Objectives: To describe and interpret the pattern of diabetes and ischemic heart disease among Yemenite immigrants in Israel and their second-generation offspring.

Methods: Medical record charts of adult Yemenites were surveyed in a primary care health center, and the data were compared with prevalence rates derived from a non-Yemenite population.

Results: There was a marked excess of non-insulin dependent diabetes mellitus among Yemenite immigrants over 45 years of age, but not of hypertension or ischemic heart disease. Yemenites with diabetes were far less likely to develop ischemic heart disease than non-Yemenites with diabetes (odds ratio for non-Yemenites compared with Yemenites, 3.5; confidence interval 1.54<OR<7.77).

Conclusions: There was less of an association between diabetes and ischemic heart disease among Yemenites. This finding requires further investigation of the relative roles of genetic and environmental factors. 

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OR= odds ratio

Background: Despite current treatment protocols, the long-term complications of insulin-dependent diabetes mellitus have prompted the investigation of strategies for the prevention of IDDM.

Objectives: To investigate the effect of oral vanadate in reducing diabetes type I in non-obese diabetic mice.

Methods: Sodium metavanadate, 3.92 mmol/L, was added to the drinking water of 8-week-old female NOD mice. Blood glucose levels, water consumption and body weight were measured, and the end point of the study was judged by the appearance of hyperglycemia in the mice.

Results: Treatment with vanadate did not significantly reduce the incidence of type I diabetes as compared to the control group. However, oral vanadate therapy significantly reduced the blood glucose levels after the fourth week of treatment compared to the control group (3.83±10.67 vs. 4.44±10.83 mmol/L, P<0.03). There was a consistent and significant increase in body weight of the vanadate-treated pre-diabetic NOD mice compared to the controls. Diabetic mice treated with vanadate had significantly lower levels of serum insulin as compared to control diabetic mice (104±27 vs. 151±36 mol/L, P<0.03). Histologically, no significant differences were found in inflammatory response of the islets of Langerhans between the control and treated groups.

Conclusions: This study suggests that the post-receptor insulin-like effect induced by vanadate is not sufficient to prevent the development of diabetes and insulitis in pre-diabetic NOD mice.

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IDDM= insulin-dependent diabetes mellitus

NOD= non-obese diabetic

Methods: We attempted to investigate plasma oxidation and plasma and erythrocyte glutathione and glutathione enzymes in 20 patients with NIDDM, compared with euglycemic matched controls. Plasma oxidation was analyzed both basally (without) and as induced by 2,2'-azobis,2-amidopropane hydrochloride measured by the generation of thiobarbituric acid reactive substances and lipid peroxides.

Results: There was a significant increase in oxidation both basally (without) and as induced by AAPH. Plasma glutathione was lowered by 50% (P<0.01) and erythrocyte glutathione peroxidase, glutathione s-transferase and glutathione reductase activities were lower by 30%, 27% and 46%, respectively (P<0.01) in the patients with NIDDM.

Conclusions: Confronted by increased oxidation, patients with NIDDM show an abnormal plasma and erythrocyte antioxidative capacity, which may result in an accelerated rate of complications.

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NIDOM= non-insulin-dependent diabetes mellitus