Israel Medical Association Journal

Background: The introduction of more potent statins such as atorvastatin and rosuvastatin in Israel was accompanied by massive advertising about their superiority.

Objectives: To assess the need for switching therapy from older statins to more potent ones among diabetic patients with uncontrolled hypercholesterolemia.

Methods: Data on all diabetic patients over 30 years old attending two urban clinics were extracted and analyzed. For each patient we checked the last low density lipoprotein-cholesterol measurements for the year 2006, the brand and the dose of cholesterol-lowering medications, prescriptions and actual purchasing over a 4 month period prior to the last LDL-C[1] measurement, and whether treatment changes were necessary to achieve the LDL-C target (100 mg/dl or 70 mg/dl).

Results: The study population comprised 630 patients, age 66.7 ± 12.6 years, of whom 338 (53.6%) were women. Of the 533 (84.6%) patients whose LDL-C was measured in 2006, 45 (8.1%) had levels < 70 mg/dl and 184 (33.3%) had levels of 70 mg/dl < LDL-C < 100 m/dl.  The reasons for LDL-C > 100 mg/dl were patients not prescribed cholesterol-lowering drugs (38.3%), partial compliance (27.2%), and under-dosage of statins (15.4%); only 7.7% needed to switch to a more potent statin. Reasons for LDL-C > 70 mg/dl were patients not prescribed cholesterol-lowering drugs (34.3%), partial compliance (22.0%), and under-dosage of statins (26.6%); only 8.7% needed to switch to a more potent statin.

Conclusions: Only a small minority of diabetic patients with uncontrolled hypercholesterolemia need one of the potent statins as the next treatment step. More emphasis on compliance and dose adjustment is needed to achieve the target LDL-C level.

Background: Idiopathic frozen shoulder is a self-limiting regional skeletal problem of unknown etiology. Clinically, patients first experience a phase of pain, progressing to a freezing stage when glenohumeral motion is lost, followed by a thawing phase when pain gradually subsides and most of the lost motion returns.

Objectives: To identify possible specific and non-specific risk factors for idiopathic frozen shoulder.

Methods: We compared the medical histories, drug treatment, previous hospital as well as health management organization blood tests of 126 new consecutive frozen shoulder patients from a shoulder clinic to those of an age-matched control group of 98 consecutive patients from an orthopedic foot and ankle clinic and to the regional population disease prevalence registry. Frozen shoulder was classified as idiopathic only if there was no history of trauma and no evidence of a rotator cuff tear.

Results: Among the frozen shoulder patients 29.4% had diabetes and 13.5% had thyroid disorders. The risk ratio for diabetes in the frozen shoulder group was 5.9 for males (95% confidence interval 4.1–8.4, P < 0.001) and 5.0 for females (95% CI[1] 3.3–7.5, P < 0.001). The risk ratio for thyroid disorders among females with frozen shoulder was 7.3 (95% CI 4.8–11.1, P = 0.001). No significant difference was found in the prevalence of thyroid disorders between frozen shoulder and the control group, but there was a significantly higher prevalence of diabetes in males and a trend for higher prevalence in females in the frozen shoulder group.

Conclusions: Physicians should be aware that diabetes is a specific risk factor for idiopathic frozen shoulder in both males and females and thyroid disorders are a non-specific risk factor in females only.  

Background: Standard CD44 and its alternatively spliced variants were found to be associated with the metastatic potential of tumor cells and with cell migration of autoimmune inflammatory cells, including cells involved in experimental insulin-dependent diabetes mellitus.

Objectives: To investigate whether induction of anti-CD44 immune reactivity, through cDNA vaccination, could attenuate IDDM[1] in a transfer model of NOD mice.

Methods: Our vaccination technique involved the insertion of CD44s[2] or CD44v[3] cDNA into a silicone tube filled with a 2.5 cm long segment of hydroxylated-polyvinyl acetate wound dressing sponge (forming a virtual lymph node) which was implanted under the skin of male NOD recipients reconstituted with diabetogenic spleen cells of female NOD donors. The VLN[4] were implanted 20 days before and 3 days after cell transfer.

Results: In contrast to control groups of recipient mice, recipients vaccinated with VLN loaded with CD44v or CD44s cDNAs developed resistance to IDDM almost to the same extent. Our results suggest that the gene vaccination effect was mediated by anti-CD44 antibody rather than by cellular immunity. Histopathological examinations revealed a significant protection of pancreatic islets in the DNA-vaccinated recipients, whereas the islets of control recipients of diabetogenic cells were almost totally destroyed.

Conclusions: These findings may open new opportunities for IDDM therapy in the future.

Background: Diabetes mellitus is associated with microvascular and macrovascular diseases, potentially manifested as endothelial dysfunction. In adults with type 2 diabetes the haptoglobin genotype 1-1 has been shown to have a protective role in inhibiting the development of complications. Although complications from type 1 diabetes are infrequent during childhood, endothelial dysfunction, which is an early marker of vascular complications, may occur.

Objectives: To evaluate endothelial function in adolescents with type 1 diabetes before the development of complications and to test for potential relationships between endothelial dysfunction and haptoglobin genotype.

Methods: The study group comprised 15 adolescents with type 1 diabetes. All underwent a general physical examination, diabetes control evaluation (including HbA1c levels), endothelial function assessment and haptoglobin genotype determination.

Results: There was a significant negative correlation between HbA1c levels and endothelial function (r = -0.48, P < 0.05), and HbA1c was significantly higher in patients with endothelial dysfunction than in those with normal endothelial function (9.9 ± 2.2 vs. 7.7 ± 1.0 mg/dl, P < 0.05). In addition, there was a tendency toward a positive correlation between high density lipoprotein and endothelial function (r = 0.4, P < 0.1). There was no correlation between the haptoglobin genotype and endothelial function.

Conclusions: These results show that even in patients without complications, uncontrolled type 1 diabetes is associated with endothelial dysfunction, which may lead to microvascular complications in the future.
 

Background: Most Israeli males aged 16–17 undergo a thorough medical examination prior to recruitment into the army. During the last 50 years, extensive data have been gathered enabling a study of time trends in the prevalence of common diseases in this age group.

Objectives: To examine the current prevalence of common diseases, compare the results with those of previous cohorts, and assess the influence of the massive immigration during the 1990s.         

Methods: The health examination at the recruitment centers includes a medical history, complete physical examination, and review of medical documentation provided by the family physician. If needed, additional tests and referral to specialists are ordered. The prevalence of selected diseases and severity was drawn from the computerized database of the classification board. Two cohorts, 1992–94 and 2003–04, were examined and compared with three previous cohort studies in 1957–61, 1977–78 and 1982–84. Data were stratified according to origin and country of birth.

Results: The prevalence of asthma increased dramatically during the years from 10.2 per 1000 examinees in 1957–61 to 111.6 per 1000 examinees in 2003–04. The prevalence of tuberculosis declined and then increased from 0.6 per 1000 adolescents in 1982–84 to 2.4 per 1000 adolescents in 2003–04. The prevalence of type 1 diabetes mellitus increased from 0.2 cases per 1000 examinees in 1957–61 to 0.8 cases in 1977–78 and 1982–84 and 0.9 cases per 1000 examinees in 2003–04. The prevalence of severe heart defects and severe epilepsy declined in the last 20 years (1.4 and 1.7 cases per 1000 examinees in the 1982–84 cohort to 0.4 and 0.3 cases per 1000 examinees in the 2003–4 cohort respectively). The patterns of disease prevalence were different for immigrants: tuberculosis was more common while asthma and allergic rhinitis were less prevalent.

Conclusions: The prevalence of common diseases among adolescents in Israel has changed over the last 50 years. There is a different pattern for immigrants and for those born in Israel.

Objectives: To evaluate the quality of care of diabetic patients in primary care and diabetes clinics in the community in central Israel.

Methods: We conducted a retrospective cross-sectional study of a random sample of 209 diabetic patients in a district of the largest health management organization in Israel. Patients were divided into two groups – those treated only by their family physician and those who had attended diabetes clinics. Data included social demographics, medications, risk factors, quality of follow-up, laboratory tests, quality of diabetes control and blood pressure control, and complications of diabetes.

Results: Of the 209 patients 38% were followed by a diabetes clinic and 62% by a family physician. Patients attending the specialist clinic tended to be younger (P = 0.01) and more educated (P = 0.017). The duration of their diabetes was longer (P < 0.01) and they had more diabetic microvascular complications (P = 0.001). The percentage of patients treated with insulin was higher among the diabetes clinic patients (75% vs. 14%, P = 0.0001). More patients with nephropathy received angiotensin-converting enzyme inhibitors in the diabetes clinic (94% vs. 68%, P = 0.02). Follow-up in the specialist clinic as compared to by the family physician was better in the areas of foot examination (P < 0.01), fundus examination (P = 0.0001), and hemoglobin A1c testing (P = 0.01). On a regression model only fundus examination, foot examination and documentation of smoking status were significantly better in the diabetes clinic (P < 0.05).

Conclusion: There is still a large gap between clinical guidelines and clinical practice. Joint treatment of diabetes patients between the family physician and the diabetes specialist may be a proposed model to improve follow-up and diabetes control. This model of treatment should be checked in a prospective study.

Objective: To assess the prevalence of diabetes in an Arab community, the contribution of obesity to diabetes development, and the therapeutic potential of a preventive program.

Methods: Data were obtained from the medical files of diagnosed diabetes patients attending a primary care clinic in an Arab village in northern Israel.

Results: Type 2 diabetes was diagnosed in 323 patients of whom 63% were women. The prevalence of diabetes below age 65 years was significantly higher among women than men. Diabetic women were younger than men at diagnosis (48.27 vs. 59.52 respectively) and were found to have higher body mass index (34.35 vs. 30.04 respectively) at diagnosis. The age at diagnosis of diabetes was strongly correlated with BMI[1] (r = 0.97, P < 0.0001).

Conclusions: Women of Arab origin are at higher risk of developing type 2 diabetes compared to men. Obesity in women seems to be associated with higher diabetes risk as well as earlier appearance of the disease. Therefore, they will have the disease for longer and, consequently, a higher risk for complications.

Objectives: To compare the seasonality of children with T1DM in different populations around the world for which data were available.

Methods: We analyzed large cohorts of T1DM patients with a clinical disease onset before age 14 or 18 years.

Results: We found a seasonality pattern only in ethnically homogenous populations (such as Ashkenazi Jews, Israeli Arabs, individuals in Sardinia and Canterbury, New Zealand, and Afro-Americans) but not in heterogeneous populations (such as in Sydney, Pittsburgh and Denver).

Conclusions: Our findings attempt to explain the controversial data in the literature by showing that ethnically heterogeneous populations with a mixture of patients with various genetic backgrounds and environmental exposures mask the different seasonality pattern of month of birth that many children with diabetes present when compared to the general population.

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.