ארדון רובינשטיין, אלנה יצחקוב

האגודה הישראלית לסוכרת

חולים הלוקים בסוכרת מסוג 2 מצויים בסיכון של פי 2-4 ללקות בטרשת-עורקים ובאוטם שריר-הלב ובשכיחות-יתר לתמותה בעת אירוע של אוטם שריר-הלב ואחריו. שיעור התמותה ממחלת לב בחולי סוכרת דומה לזו של אוכלוסייה שאינה לוקה בסוכרת, ושחוותה אוטם בעבר. ב- 80%-75% מהלוקים בסוכרת מתים מטרשת-עורקים וסיבוכיה. סוכרת מהווה גורם סיכון עיקרי למחלת לב ולטרשת-עורקים, ואחד הגורמים העיקריים התורמים להיותה כזו הן ההפרעות במשק השומנים, ההמלצות המובאות בזאת מהוות השלמה להמלצות למניעת מחלות לב, שפורסמו מעל דפי "הרפואה" בגיליון הראשון של המילניום.

(1) אלנה יצחקוב, (2) ארדון רובינשטיין

(1) המח' לרפואה פנימית ה', (2) המכון למטאבוליזם ביה"ח איכילוב, תל-אביב

השכיחות של מחלת לב איסכמית בחולי סוכרת מסוג 2 גדולה פי 2-4 מכלל האוכלוסייה, והתמותה בחולי סוכרת עם טרשת עורקים עקב מחלת לב איסכמית גדולה פי 3-6 מכלל האוכלוסייה. כ-80%-75% מהחולים בסוכרת מסוג 2 נפטרים מטרשת עורקים ומסיבוכיה.

סוכרת מהווה גורם סיכון עיקרי לטרשת עורקים והפרעות במשק השומנים (lipids) והליפופרוטאינים הם מהגורמים העיקריים לסוכרת. בסוכרתיים, כמו בלא סוכרתיים, יכולות רמות שומנים גבוהות להיות קשורות למצבים שאינם קשורים להיפרגליקמיה ולתינגודת לאינסולין, כמו לדוגמה, מחלת כליות, תת תריסיות, מחלת כבד או הפרעות גנטיות במשק הליפופרוטאינים.

ג'מאל עווד¹, בלה שינדל², יאיר שינדל¹

¹המח' לרפואה פנימית ו', ביה"ח לגליל המערבי, נהריה, ²מירפאת סוכרת, מרכז רפואי רבין, פתח-תקוה

האירגון האמריקאי לסוכרת (The American Diabetes Association - ADA) – ממליץ, שאם לא הושג איזון של הסוכרת בחולים NIDDM תוך שלושה חודשים על ידי תזונה דלת-סוכר והתעמלות, יש להתחיל בטיפול תרופתי. בדרך כלל מומלץ להתחיל בתרופה פומית אחת המורידה את רמת הסוכר, כמו, לדוגמה, (s‘SLP) sulfonylureas, (MTF) metformin, (ACS) acarbose או אינסולין.

בבחירת התרופה, יש לדעת את הפתוגנזה העיקרית שהביאה להיפרגליקצמיה, מנגנון הפעולה של התרופה, מחירה, השפעות-הלוואי, אופן מתן התרופה ומידת הדחיפות להורדת רמת הסוכר, דהיינו, ההסתמנות הקלינית של החולה.

התרופות מקבוצת ה- sulfonylureas הן השימושיות ביותר היום כטיפול התחלתי. Metformin מקבוצת ה- biguanides הוא תרופה מהקו הראשון לטיפול בחולי NIDDM הלוקים בהשמנת-יתר ועמידות לאינסולין. התרופה יעילה במיוחד במישלב עם תרופה מקבוצת ה- sulfonylureas, במיוחד במצבים בהם ה- s‘SLP בלבד לא הביאו לאיזון החולה.

התרופה החדשה יחסית acarbose מקבוצת האלפא glucosidase מפחיתה בצורה ברירנית את עליית הגלוקוזה לאחר הארוחה, ואין לה כמעט השפעה על רמת הסוכר בצום. שתי הקבוצות שהוכנסו לשימוש רק לאחרונה הן:

קבוצת ה- thiazolidinedione (troglitazon, rosigltazon) מגבירה את רגישות הרקמות ההיקפיות לאינסולין, כלומר, "מעוררת" תגובה חזקה יותר לאינסולין בשריר, בריקמת השומן ובכבד.

קבוצת ה- meglitinides (repagilinide) מגבירה את הפרשת האינסולין מהלבלב בדומה לקב' ה- s‘SLP, אלא שהשפעתה מהירה יותר וקצרה יותר, ומתאימה להפחתת רמות הגלוקוזה בנסיוב לאחר ארוחה.
 

Diabetes and Premature Delivery: Etiology and Risk Factors 

Avi Beigelman, Arnon Wiznitzer, Ilana Shoham-Vardi, Hilel Vardi, Gershon Holtcberg, Moshe Mazor

Depts. of Obstetrics and Gynecology and of Epidemiology and Health Services Evaluation, Soroka Medical Center and Faculty of Health Science, Ben-Gurion University of the Negev, Beer Sheba

Preterm birth is the leading cause of perinatal morbidity and mortality, while preterm labor and delivery in diabetes mellitus (DM) carries an increased risk of perinatal complications. We investigated the hypothesis that DM (gestational and pregestational) is an independent risk factor for preterm birth and evaluated the hypothesis that the risk factors for preterm birth in diabetics are different from those in non-diabetics.

The study population consisted of all singleton deliveries at this hospital between 1990-1997. Excluded were those of mothers who had not had prenatal care, or who had only partial care or multiple gestations. There were 3 subgroups: 834 women with pregestational DM, 3,841 with gestational DM, and 66,253 non-diabetics.

The combined spontaneous and induced preterm delivery rate was determined in each subgroup. Potential risk factors for spontaneous preterm deliveries were assessed by a univariate model. A logistic regression model was used to assess the unique contribution of DM (gestational and pregestational) to preterm delivery in the presence of the other risk factors, and to compare risk factors for preterm delivery between subgroups.

The prevalence of spontaneous preterm delivery was: 7.1% in non-diabetics, 10.0% in those with gestational DM and 25.5% in those with pregestational DM. When adjusted by a multivariate model for other risk factors for preterm delivery, DM still remained an independent risk factor for spontaneous preterm delivery (gestational DM: odds ratio 1.28, 95% CI: 1.1-1.48; pregestational diabetes: odds ratio 3.4, 95% CI: 2.65-4.36).

The main difference in risk factors for preterm birth between the 3 subgroups was the amount of amniotic fluid. Polyhydramnios was an independent risk factor for preterm delivery in non-diabetics and in pregestational DM, but not in gestational DM. On the other hand, oligohydramnios was associated with a higher risk for preterm delivery only in gestational DM compared to non-diabetics.

DM (gestational and pregestational) is an independent risk factor for spontaneous preterm delivery. Polyhydramnios is an independent risk factor for preterm delivery in pregestational but not in gestational DM. Oligohydramnios is a greater risk factor for preterm delivery in gestational DM compared to non-diabetics.

Family Physicians' Attitudes to Clinical Guidelines for Treatment of Diabetes 

Sasson Nakar, Shlomo Vinker, Tal Baro-Aloni, Eliezer Kitai

Dept. of Family Medicine, Rabin Medical Center and Sackler Faculty of Medicine, Tel Aviv University

Clinical guidelines are systematically developed statements designed to help practitioners and patients make decisions about appropriate health care for specific clinical states. Attitudes of family physicians to clinical guidelines for treating diabetes and guidelines in general were evaluated from anonymous questionnaires answered by physicians participating in continuous medical education throughout the country (May-June 1998). The questionnaire dealt with attitudes to the recently published specific guidelines for treating the diabetic patient and overall perception of the efficacy of clinical guidelines.

293 family physicians, aged 40.2‏7.0 responded (83%). 93.5% appreciated the guidelines and thought them applicable. Most (83.7%) reported the guidelines to be of help in their daily work; 31.4% said they were oversimplified; a quarter said they aimed main at containing costs. Most respondents preferred written guidelines of up to 5 pages.

In view of our results, attention can now be turned to developing ways to implement the guidelines. To improve adherence, they need to be short and the rate of publication of new clinical guidelines should be slowed.

SYME Amputation for Foot Infections in Diabetics 

Michael Michailevich, Ehud Lebel, Menachem Itzchaki

Dept. of Orthopedics, Shaare Zedek Medical Center, Jerusalem

Syme ankle disarticulation for foot infections in diabetics with concomitant peripheral vascular disease is often unsuccessful. The need for re-amputation usually results from recurrent infection or ischemia of the posterior heel flap. We present 5 such cases of deep foot infections in diabetics who underwent Syme amputation after failure of local debridement. All patients needed reamputation in 4-18 days for ischemia of the flap.

Type 2 Diabetes among Adolescents in Israel 

Orit Pinhas-Hamiel, Ilana Koren, Pnina Vardi

Maccabi Juvenile Diabetes Center, Ramat Hasharon and Lin Diabetes Center, Haifa

Type 2 diabetes has been considered rare in children and adolescents. Recently, increase in the incidence of type 2 diabetes has been reported among adolescents in various parts of the world. We report the occurrence of type 2 diabetes among adolescents in Israel.

A boy of 14 and girls of 16.5 and 17 were pubertal and extremely obese, with a body mass index (BMI) between 39-47 kg/m². Acanthosis nigricans, elevated diastolic blood pressure, and hirsutism with menstrual disorders, were associated with insulin resistance, and should raise suspicion of type 2 diabetes. Significant obesity and strong family histories of type 2 diabetes appeared to be important risk factors. Since type 2 leads to long-term morbidity and mortality, its early identification and appropriate treatment are crucial.

Incidence of Insulin Dependent Diabetes in Youth in Israel 

Israel IDDM Registry Study Group

Recent reports from different countries have shown an increasing incidence of insulin-dependent diabetes mellitus (IDDM, type I diabetes). In Israel, several surveys of the incidence of IDDM have been conducted. During 1996, a national juvenile diabetes register was founded by specialists in endocrinology, and the Israel Center for Disease Control (ICDC).

This is the first report of the national incidence of IDDM in the 0-17 year age group in Israel. New cases of juvenile diabetes were reported using an anonymous form. The ICDC was responsible for data collection, control and statistical analyses.

During 1997, 162 new cases of diabetes mellitus were reported in the age group 0-17, 154 of them diagnosed as IDDM. The annual incidence in the total population of Israel in 1997 was 7.7/100,000. Age-specific incidence was 7.3/100,000 in boys and 8.1 in girls. A family history of IDDM was found in 14.3% of the cases. Incidence was higher for Jews (9.2/100,000) than Arabs (3.6/100,000). Among Jews, children whose fathers were born in Yemen had the highest incidence and those born to fathers born in Israel the lowest incidence.

IDDM incidence rates for 1997 are higher than reported in previous surveys. It will be possible to draw conclusions regarding possible trends in incidence from data to be gathered in the next few years.

Diabetic Ketoacidosis during the Ramadan Fast 

I. Friedrich, Y. Levy

Dept. of Medicine A, HaEmek Medical Center, Afula, and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa

We report a 15-year-old Muslim boy with insulin-dependent diabetes mellitus (IDDM) who presented with diabetic ketoacidosis (DKA) during the Muslim Ramadan month of day-time fasting. DKA apparently occurred due to omitting pre-lunch insulin combined with dehydration and overeating during the permitted sunset-to-sunrise meals.

It is well-known that fasting accelerates development of lipolysis and ketosis and increases glucagon levels. Thus, these pathophysiological aberrations related to fasting in ketosis-prone patients, in conjunction with fasting, endanger metabolic control in IDDM.

ACE Gene Polymorphism in a Diabetic Cohort and Diabetic Nephropathy

Orna Levinson, Shmuel Oren, Chana Yagil, Marina Sapojnikov, Alexander Wechsler, Rosanna Bloch, Yoram Yagil

Laboratory for Molecular Medicine, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba and Barzilai Medical Center, Ashkelon

The renin-angiotensin system is thought to play an important role in the pathophysiology of kidney disease in diabetes. Previous studies have shown a possible association between the D allele of the angiotensin converting enzyme (ACE) gene, known to be associated with higher circulating levels of ACE, and increased risk of developing nephropathy in NIDDM. The present study investigated the distribution of ACE gene genotypes in the general population and patients with NIDDM, the association between the D allele and diabetic nephropathy, and the association between the ACE genotype and involvement of other target organs in NIDDM. The ACE genotype (insertion/deletion I/D) was determined in all subjects, subsequently divided into 3 groups based on their polymorphism (DD, DI and II). The presence of nephropathy was defined by an albumin-creatinine ratio of 30 mg/g or greater (mean of 2 first morning urine samples).

In the general population most had the D allele (DD or ID) and a minority the II genotype. There was no association between genotype and hypertension, ischemic heart disease, hyperlipidemia, and cerebrovascular or peripheral vascular disease. In diabetics the genotype distribution was not different from that in the general population. Within the diabetic group, there was no association between genotype and hypertension, hyperlipidemia, duration of diabetes, or HbA1C levels. Nephropathy, found in 81 of the 156 with NIDDM, was not associated with genotype. Diabetic nephropathy was not associated with retinopathy, neuropathy, or ischemic heart, cerebrovascular or peripheral vascular disease. We conclude that in the population sampled, there was no association between the D allele of the ACE gene and the risk of developing nephropathy in NIDDM.

The Diagnosis and Treatment of Fournier's Gangrene

M. Cohen, E. Tamir, S. Abu-Abid, Y. Galili, M. Giladi, S. Avital, R. Shafir, Y. Klausner

Surgery and Infectious Disease Depts. and Division of Surgery, Tel Aviv-Sourasky Medical Center, and Sackler Faculty of Medicine, Tel Aviv University

We treated 2 women and 8 men suffering from Fournier's gangrene during 1990-96. 2 had diabetes, 1 suffered from ulcerative colitis and 1 was an alcoholic. In 8 of them the infection was triggered by a mixture of aerobic and anaerobic bacteria. Treatment consisted of repeated wide debridement and early colostomy. This aggressive approach resulted in relief of the septic signs within 24 hours and permitted early skin grafting of the wounds. 2 patients died due to sepsis that caused multiple organ failure. The 8 who survived were hospitalized for an average of 35 days. On follow-up examination 1-5 years later all patients had undergone closure of the colostomy and were completely rehabilitated.

Fournier's gangrene is not rare in the geriatric population. We believe that early diagnosis and aggressive wide debridement, combined with early colostomy, are the keys to successful treatment.

Islet Autoantibody Assays in Type I Diabetes can Replace ICA Test

Daniel Lazar, Naomi Weintrob, Natalia Abramov, Sara Assa, Konstantin Bloch, Regina Ofan, Hadassa Ben-Zaken, Pnina Vardi

Institute for Pediatric Endocrinology and Diabetes, Schneider Children's Medical Center, Petah Tikva and Felsenstein Medical Research Center, Tel Aviv University

Islet cell antibodies (ICA) continue to serve as the basis of the principal serological test for definition of active autoimmunity of beta-cells. Its disadvantages are the need for human pancreatic tissue and difficulty in obtaining quantitative results. In the past decade biochemically-defined beta-cell antigens were described, leading to the development of sensitive and specific autoantibody assays, to predict insulin-dependent diabetes mellitus (IDDM). We examined the value of combined biochemically-based serological assays, such as autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA) and ICA512 (ICA512A) to replace the traditional ICA assay.

Blood samples of 114 newly diagnosed IDDM patients, aged 12‏5 yrs (range 2 months - 29 years) were tested for ICA (indirect immunofluorescence), IAA, GADA and ICA512A (radiobinding assay). The latter 2 assays were performed using recombinant human [35S]-labeled antigen produced by in vitro transcription/translation. We found that fewer sera scored positive for ICA and/or IAA (80.7%, 92/114) than for 1 or more of IAA, GAD, or ICA512 (88.6%, 101/114). We conclude that combined testing for IAA, GAD and ICA512 can replace the traditional ICA/IAA test to predict IDDM and is helpful in the differential diagnosis of insulin-dependent and noninsulin-dependent diabetes.

Progression of Diabetic Retinopathy after Cataract Extraction

Y. Raniel, Y. Teichner, Z. Friedman

Annette and Aron Rozin Dept. of Ophthalmology, Bnai-Zion Medical Center and Bruce Rappaport Faculty of Medicine, The Technion, Haifa

A prospective study of the effect of cataract extraction with intraocular lens implantation on the course of diabetic retinopathy (DR) in 44 patients (59 eyes) was carried out. It showed that in the 1-3 years following surgery, there was progression of DR (including development of newly formed retinopathy) in 35% of the patients (28.8% of eyes). Progression was more marked in patients with pre-operative bilateral DR compared to those without bilateral DR (77% and 16% respectively). Insulin dependence did not play a role in progression. Final visual acuity was better in patients without pre-operative DR, as well as in eyes without progressive retinopathy.

Red Cell Na+/H+ Exchange and Role of Protein Kinase C in its Stimu-Lation in Diabetes Mellitus, Essential Hypertension and Nephropathy

Wladimir Koren, Robert Koldanov, Edna Peleg, Eva Izsak, Meir Berezin, Talma Rosenthal

Dept. of Medicine C, Hypertension Unit and Endocrinology Institute, Chaim Sheba Medical Center, Tel Hashomer

Na+/H+ exchange (NHE) was measured as maximal initial velocity of pH-dependent H+ efflux from red cells into an alkaline medium containing Na+ in patients with insulin-dependent or noninsulin-dependent diabetes, with and without hypertension and in normoglycemic, essential hypertensives and normal controls (50 subjects in each subgroup). Maximal velocities of NHE were found in microalbuminuric patients in all subgroups, and NHE correlated with the rate of microalbuminuria (r=0.61, p=0.02). Daily insulin requirements were greater in those with elevated NHE (84±8 vs 42±4 U/day). There was no correlation between NHE and levels of plasma glucose, HbA1 and plasma aldosterone and lipid profile and PRA. NHE was correlated with plasma prolactin (r=0.51, p=0.02) and PTH r=0.24, p=0.05). In uremic patients, NHE was inversively correlated with creatinine clearance (r=-0.48, p=0.03). Since calphostin C, a selective inhibitor of protein kinase C, lowered increased NHE in vitro, the protein kinase C-dependent pathway of the exchanger regulation was concluded to be responsible for NHE activation in diabetes mellitus and essential hypertension.

Efficacy and Safety of Acarbose Treatment of Niddm

Julio Wainstein, Medinah Jedwab

Dept. of Medicine C and Diabetes Unit, Wolfson Medical Center, Holon

An uncontrolled multicenter study of the efficacy and safety of treatment of diabetes with acarbose was conducted on 169 NIDDM patients in 12 medical centers in Israel. Acarbose was administered for 19 weeks, and the patients were followed for an additional 12 weeks. A substantial decrease in HbA1c levels from 8.5% to 7.5% (p<0.001) and in postprandial serum glucose levels from 283.6 mg/dl to 248.5 mg/dl (p<0.01) was seen during treatment. On follow-up, HbA1c levels increased by 0.45% and postprandial serum glucose rebounded from 256.4 mg/dl to 287.9 mg/dl. Acarbose was shown to be effective in treating NIDDM and to be safe and well-tolerated.