Iranian Journal of

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Diabetes mellitus is a common disease and its incidence and prevalence are increasing in most populations. The trend is particularly worrying in developing countries. The number of diabetic patients in Iran is estimated at 1.5 million. The distribution of diabetes in Iran has been the subject of several surveys. Disease prevalence rates, for all forms of diabetes, of 7–17% have been variously reported in several adult urban populations. Geographical prevalence is not uniform, however, and the prevalence of type 2 diabetes mellitus has been reported at 3-5% in rural communities. A screening program conducted at different locations of Iran revealed that nearly 50% of people with type 2 diabetes were unaware of their condition. Not surprisingly, therefore, that the incidence of complications for diabetes is high in Iran. A battle is being waged on all fronts at present to control the socio-economic scourge that is diabetes mellitus. A national program has been designed for the primary, secondary, and tertiary prevention of diabetes. The major strategies that it puts forwards are screening, the identification of high-risk groups, public education, and the training of specialist care providers. This article reviews the epidemiological features of diabetes in Iran.

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Diabetes during pregnancy is either concurrent diabetes, diagnosed before pregnancy, or ‘gestational diabetes mellitus’ (GDM), first diagnosed in pregnancy. GDM is the commonest metabolic disorder of pregnancy, with a prevalence of one to 14 percent, depending on the reporting team. The prevalence of GDM in Tehran is 4.7%. Diabetes concurrent with pregnancy is diagnosed according to the recently revised criteria of the National Diabetes Data Group (NDDG). GDM is diagnosed with a 100-gram 3-hour glucose tolerance test (3hGTT100), with at least two abnormally high readings being required for a definite diagnosis. Screening for GDM is still a matter of dispute. Universal or selective screening? Each has its supporters. The American Diabetes Association (ADA) recommended universal screening until 1997, and this is still recommended for areas with a high prevalence of GDM. Diabetes during pregnancy has multiple potential consequences for mother and fetus fetal macrosomia being the commonest. The children of diabetic mothers are also more likely to become overweight and develop impaired glucose tolerance. ADA recommendations for glycemic control in diabetic mothers-to-be include maintaining their fasting blood glucose between 60 and 95mg/dl, and their postprandial blood glucose between 80 and 120mg/dl. Measurement of urinary ketones is recommended when the patient is on a calorie-restricted diet. Lifestyle changes are an integral part of management. Insulin requirements and calorie intake must be adjusted in line with weight gain as pregnancy progresses.

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Background: Urtica dioica, or the stinging nettle, is recommended by ancient medical texts for the treatment of high blood sugar.
Methods: We set up a perifusion system, in which an exact number of islets of Langerhans were exposed to an active component of the leaf extract of Urtica dioica, obtained by TLC. The active component was then injected into the peritoneum of both normal and diabetic rats to evaluate response in vivo.
Results: There was a marked increase in insulin secretion in vitro, as determined by ELISA. In vivo, there was an increase in blood insulin content following intraperitoneal injection. The increase in serum insulin observed at 60 minutes was associated with a decrease in blood glucose, checked several times during the observation period. Maximum insulin release over 120 minutes was equal to five times the baseline value. The decrease in blood sugar correlated with both the timing and magnitude of insulin release.
Conclusion: Notwithstanding the magnitude of the changes observed, the results obtained in normal and diabetic rats were similar.

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Background: Estimation of cost effectiveness and cost benefit are intrinsic to the design and evaluation of healthcare systems. The aim of most studies of gestational diabetes screening has been to modulate screening parameters to reduce the eligible population and therefore costs. We analysed the findings of a cross-sectional study of gestational diabetes mellitus carried out in Tehran to determine the screening method best suited to the socio-economic profile of our population.
Methods: 2416 pregnant women were universally screened in Tehran teaching hospitals. Each patient’s risk factors and laboratory results were recorded. The 50gGCT was used to screen and the 100gOGTT to confirm a diagnosis of GDM.
Results: Switching from the 130mg/dl to the 140mg/dl threshold, case-detection sensitivity declined by 12% (to 88%), with the per-pregnancy cost dropping from 30,410 to 25,641 Rials (from US$3.80 to 3.20) [-15.6%], and the cost per detected case from 644,488 to 619,500 Rials (from US$80.56 to 77.43) [-3.87%].
Conclusion: We recommend adoption of the universal screening approach in Iran for 4 reasons: (1) The high prevalence of gestational diabetes in the low-risk group (2) The poor level of healthcare provided in Iran compared with societies that have opted for the selective approach (3) The lower cost of screening and diagnostic tests in Iran compared with the aforementioned and (4) The high cost of treating the complications of diabetes.

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Background: Numerous studies have confirmed the association between type 1 diabetes mellitus (DM1) and polymorphisms of HLA genes on chromosome 6p21. Controlled DNA studies in Belgium recently have found a statistically significant association between DM1 and certain HLA class II genes, especially DRB1Lys71+.
Methods: 81 Danish families (each with at least 2 members with DM1) and 82 healthy controls were assessed for HLA polymorphisms. 54 of the 81 diabetic families were also assessed for polymorphisms at the HLA-B-DQB1, HLA-B-DQA1, and TNF-A and TNF-B loci. Affected sib-pair analysis was used to study correlation between DM1 and DRB1 alleles encoding Lys71+.
Results: Homozygous expression of DRB1Lys71+ carried a relative risk (RR) of 103.5 for DM1. There was a very strong correlation (p<1×10-6) between DM1 and DRB1 alleles encoding Lys71+. Family-based association studies showed that DRB1Lys71+ was the most important determinant of DM1 in carriers (haplotype relative risk = 8.38). Haplotype analysis confirmed this.
Conclusion: The DRB1Lys71+ allele confers genetic predisposition to DM1 most strongly of all.

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Background: Studies of the metabolic effects of Ramadan fasting on patients with type 2 diabetes mellitus are inconclusive.
Methods: Fifty-seven volunteers with type 2 diabetes underwent anthropometric and biochemical evaluation before and on the 14th and 28th days of Ramadan. Biochemical markers were measured by standard laboratory methods. Anthropometric measurements followed WHO criteria. Statistical analysis was by ANOVA for repeated measurements and Friedman’s two-way ANOVA, using SPSSv6 software.
Results: Daily cholesterol intake increased in all subjects (p<0.03). Body mass index increased (p<0.03) in women, but body mass index (BMI) and waist-to-hip ratio both decreased (p<0.01) in men. Blood pressure, fasting blood glucose and serum fructosamine did not change during the study. Plasma insulin (p<0.05), C-peptide (p<0.01) and insulin resistance (p<0.01) decreased only in men. Total and LDL cholesterol increased significantly in all subjects during the study.
Conclusion: Ramadan fasting does not alter carbohydrate metabolism or tissue insulin sensitivity in type 2 diabetes patients, given appropriate dietary education and rescheduling of oral hypoglycaemic medication. Lipid profile is unfavourably altered due to changes in both diet and biochemical response to starvation. Anthropometric indices improve in men but not women, possibly because of reduced physical activity in the latter.

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Background: Oral glucose tolerance testing (OGTT) is the gold standard for the diagnosis of diabetes mellitus and impaired glucose tolerance (IGT), but is time-consuming and difficult to perform. We investigated the value of glycosylated hemoglobin (HbA1C) in screening for diabetes mellitus and IGT.
Methods: In a cross-sectional study, we measured the HBA1C levels of 497 people referred for OGTT. We calculated the sensitivity and specificity of HbA1C at 1, 2, 3 and 4 SD above the normal mean. We plotted receiver operating characteristic (ROC) curves after assigning our subjects to the diabetic, IGT, ‘diabetic+IGT’, or normal group, based on WHO criteria for OGTT.
Results: HbA1C levels (mean ± SD) in the four groups were 9.2±1.5, 8.4±1.3, 7.9±0.8 and 6.8±0.7 percent in the diabetic, diabetic+IGT, IGT and normal groups, respectively. All differences were statistically significant (p<0.0001). ROC curve analysis showed that HbA1C levels above 7.5% (mean + 1SD) gave the best combination of sensitivity and specificity for the detection of diabetes (97.53% and 73.8%), IGT (66.37 and 69.44%), and diabetes+IGT (80.22% and 86.66%).
Conclusions: An HbA1C level of >7.5% is an optimal cutoff point for diabetes screening programs.

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Background: The American Heart Association used the findings of the Framingham Heart Study to design an equation that quantifies the risk of coronary heart disease (CHD).
Methods: The variables in this equation are age, total cholesterol, HDL-cholesterol, systolic blood pressure, cigarette smoking, diabetes mellitus and evidence of left ventricular hypertrophy on electrocardiography. We calculated the CHD risk of 139 patients, with type 2 diabetes mellitus, who attended our diabetes clinic. We also assessed risk factors not taken into account by the Framingham equation, such as obesity (body mass index (BMI) or waist-hip ratio (WHR)), plasma triglyceride, LDL-cholesterol (LDL-C), and diastolic blood pressure (DBP). We used the linear regression and one-way ANOVA functions on the SPSS.v6 software to analyze our data.
Results: Ninety-one women and 48 men enrolled in the study. Men had a higher five- and ten-year CHD risk than women. 36.4% of our subjects had plasma HDL-C <35mg/dl. The TC:HDL-C ratio was 6.18±1.76 in men and 5.97±2.21 in women. We found no significant correlation between two- and five-year CHD risk and WHR, BMI or triglyceride levels. There was a significant correlation between two- and five-year CHD risk and DBP (p=0.0006 and p=0.0001) and LDL-C (p=0.005 and p=0.001).
Conclusion: Patients with diabetes mellitus have a higher, but smaller than expected, risk of CHD. The value of the Framingham equation in diabetic patients is equivocal, given the absence of correlation between obesity markers and CHD risk. Larger, prospective, studies are needed to clarify the matter.

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Background: Diabetes mellitus is a common chronic disorder with multiple disabling long- and shorter-term complications, the majority of which can be controlled if not prevented. The management of diabetic patients is a major drain on both health budgets and time.
Methods: We reviewed the records of 101 patients with diabetic foot ulcer, who had received treatment at either Doctor Shariati or Imam Khomeini hospital.
Results: Out of 101 patients (56.4% male and 43.6% female) with diabetic foot ulcer, 34.7% had eventually undergone amputation.
Conclusion: Our findings highlight the need for control and prevention programmes aimed at reducing the risk factors for and complications of diabetic foot ulcer.

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The incidence and prevalence of type2 diabetes mellitus is increasing worldwide. Many believe that type 2 diabetes mellitus is a disease that can be prevented by appropriate interventions in individuals at high risk for the disease. A number of studies have therefore looked at primary prevention during the past decade. Iran’s diabetic population of approximately 2 million people and the warning by the World Health Organisation that diabetes is on the rise in developing countries make the primary prevention of diabetes mellitus in Iran doubly important. Researchers have been increasingly focusing on identifying the risk factors for type 2 diabetes and, through these, appropriate strategies to prevent the rapidly growing incidence of this disease in the population at risk. Genetic predisposition (a positive family history), insulin resistance, obesity, impaired glucose tolerance, a history of gestational diabetes mellitus, physical inactivity and an unsuitable diet are among the most important recognised risk factors for type 2 diabetes other factors have also been found to contribute. Most of the available research has evaluated the effect of behavioural or lifestyle modification, in the form usually of dietary education and increased physical activity, in the primary prevention of type 2 diabetes. The second most common approach has been pharmacological manipulation. The information available indicates that type 2 diabetes will come to be considered as a preventable disease within the next decade. The weight of research behind this problem will undoubtedly discover even more effective methods of preventing type 2 diabetes in the near future than behavioural/lifestyle modification.

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There are more than 140 million people with diabetes in the world. Iran’s share is estimated at 1.5 million people. The increasing prevalence of diabetes and the longer life expectancy of diabetic patients mean that an increasing number of patients with diabetes are undergoing surgery, and not just for diabetes and its complications, such as end-stage renal disease, retinopathy, peripheral vascular disease, and diabetic foot ulcers. The metabolic stress caused by general anaesthesia and the operation itself makes blood glucose control even more difficult. Stricter pre- and intra-operative glycaemic control reduces the risk of sepsis, cardiovascular events, disability and death, accelerates wound healing and decreases hospital stay. Improved outcome requires pre-operative ascertainment of the type of diabetes, quality of metabolic control, and detection of complications, as well as optimal metabolic and haemodynamic management during the operation. Local anaesthesia is the preferred option in this group of patients because it least interferes with metabolic control. The diet recommended to achieve normoglycaemia will depend on the type of diabetes, pre-operative glycaemic control, and the extent of the planned procedure. In all type 1 diabetic patients and type 2 diabetic patients on insulin or oral hypoglycaemic agents who are to undergo surgery under general anaesthesia, the glucose-insulin-potassium (GIK) regimen is the one recommended by most authors to achieve tight intra-operative blood glucose control, conditional upon blood glucose measurements being available every one or, at most, two hours. Intra-operative blood glucose levels in the 120-180mg/dl ranges are considered satisfactory. Failing this, it is recommended that 50% of the daily NPH requirement be given subcutaneously on the morning of the operation, together with an intravenous glucose infusion intra-operatively. Type 2 diabetic patients with unsatisfactory metabolic control, time permitting, should be admitted several days before the operation and switched to and stabilised on insulin.

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Introduction: The prevalence of type 2 diabetes is increasing daily all around the world and is a serious threat to the well-being of the community in terms of renal failure, cardiovascular disease, blindness, and neuropathy. The assessment of difference screening approaches is of great importance in this disease. We compared ADA and WHO criteria for the diagnosis of type 2 diabetes.
Methods: 982 individuals (age range: 30 to 64 years), residents of the city of Bushehr, were chosen by systematic random sampling for this study, each providing a fasting blood sample for a standard oral glucose tolerance test. Plasma glucose was measured by the glucose oxidase-peroxidase method, using a Technikon RA1000 autoanalyser. Data was analysed with the Chi-squared and Student’s t tests and, when required, Fisher’s Exact test.
Results: 354 (36%) men and 628 (64%) women took part in this study. 42.9% were in the 30-39 age group. 69 (20 men and 49 women) of the 982, that is 7% of the sample, had known diabetes before recruitment into the study. The crude prevalence of type 2 diabetes and impaired glucose tolerance using WHO criteria was 13.6 and 15.6 percent, respectively. The crude prevalence of type 2 diabetes using ADA criteria was 13.4 percent. 51% of patients were already aware of their disease. The sensitivity of fasting blood glucose testing for detecting diabetes was 45.8% using WHO and 62.5% using ADA criteria. Both sets of criteria were equally specific.
Conclusion: Given the overall prevalence of glucose intolerance (impaired glucose tolerance and type 2 diabetes) in Bushehr, it should be considered as a high-prevalence area for diabetes. Accordingly, we recommend screening with fasting plasma glucose and oral glucose tolerance testing.

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Introduction: In order to determine the relationship between serum lipid profile and diabetes mellitus as well as other cardiovascular risk factors, we carried out a cross-sectional study of 1255 oil industry workers at the Kharg Island oil terminal.
Methods: Increased levels of total cholesterol (TC≥200mg/dl), triglyceride (TG≥200mg/dl), and low-density lipoprotein (LDL≥130mg/dl) were seen in 32.7%, 39.5% and 18.5% of the workers, respectively. Decreased levels of high-density lipoprotein (HDL<40mg/dl) were seen in 13.1% of workers. 61.3% of the workers had a body mass index (BMI) ≥25kg/m2. Visceral obesity (waist circumference >100cm) was seen 32.4% of workers.
Results: There was a direct and significant relationship between TC levels and BMI (p<0.001), and between TG levels and BMI (p<0.0001). The same correlation existed between waist circumference and both TC (p<0.02) and TG (p<0.06). There was also a direct correlation between LDL levels and waist circumference (p<0.04). 10.6% of workers had some disorder of glucose metabolism. There was a direct correlation between diabetes and both TC and HDL levels (p<0.04 and p<0.05, respectively). 42.4% of workers smoked and 57.4% had a sedentary lifestyle. There was a trend toward lower blood glucose and cholesterol levels as the level of physical activity increased (p=0.1 and p=0.08, respectively). There was a significant difference between blue- and white-collar workers in the prevalence of excess weight, visceral obesity, diastolic hypertension, diabetes and cigarette smoking, but not serum lipid profile and level of physical activity.
Conclusion: The significant prevalence of dyslipidaemia and other cardiovascular risk factors in the oil workers of Kharg Island requires systematic preventive interventions to reduce cardiovascular mortality and morbidity in this population.

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Introduction: In patients with type 2 diabetes, triglyceride (TG) is usually increased, HDL decreased, and LDL normal. This pattern is associated with an increased risk of coronary heart disease. More recently, dense-particle LDL has been identified as an important risk factor for coronary heart disease.
Methods: 298 patients with type 2 diabetes attending the diabetes clinic at Doctor Shariati University Hospital underwent anthropometric and biochemical assessment. Anthropometric measurements followed WHO criteria. Biochemical indices (apoB100, TG, cholesterol, LDL, LDL particle size, HDL, and apoA1) were measured using standard laboratory methods. One-way ANOVA was used to analyse data with SPSSv6 software.
Results: Mean patient age was 55±13.2 years. Mean duration of diabetes was 9.5±6.1 years. The majority of patients were moderate to severely overweight. 73.2% of patients had some form of hyperlipidaemia. 20.7% had isolated hypertriglyceridaemia, 21% isolated hypercholesterolaemia, and 31.5% mixed hyperlipidaemia. Mean apoA1 concentration was higher than normal in this group, and mean apoB100 concentration lower. LDL particle size generally followed a small and dense pattern.
Conclusion: This study shows that LDL particles in both men and women with type 2 diabetes undergo both qualitative and quantitative changes. 35.5% of patients had smaller, denser LDL particles than normal. It appears that dyslipidaemia and B-pattern LDL particles are important risk factors for atherosclerosis in this group.

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Introduction: Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance occurring or detected for the first time during pregnancy. Hypertension occurring as a result of pregnancy is called pregnancy-induced hypertension (PIH), which is itself divided into two groups: gestational hypertension and pre-eclampsia. The aim of this study is to compare the incidence of hypertensive disorders in patients with GDM and controls.
Methods: This is a case-control study of 2416 pregnant women attending 5 antenatal clinics attached to Tehran University of Medical Sciences. The universal two-step screening approach was used: first, all women underwent a 50-gram 1-hour glucose challenge test second, all women with a 1-hour blood glucose concentration higher than 130mg/dl underwent a 100-gram, 3 hour oral glucose tolerance test. Carpenter and Coustan’s criteria were used to diagnose GDM. 220 women with a normal glucose challenge test were chosen as controls. GDM cases and controls were matched for age, body mass index, parity, and gestational age.
Results: 114 women overall were diagnosed with GDM. Mean age, BMI, and parity in GDM and control groups were 29.09±6.13 and 28.64±6.00 years, 27.43±4.33 and 26.64±1.8 kg/m2, and 1.79 and 1.52 births, respectively. Women with GDM had a higher prevalence of essential hypertension, PIH, and pre-eclampsia than matched controls.
Conclusion: Our results show that hypertensive disorders are more common in women with GDM than in normoglycaemic controls of similar age, parity and BMI.

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In this article, we review animal models of types 1 and 2 diabetes mellitus. Models of type 1 diabetes are discussed in two parts, genetic and chemical. Models of type 2 diabetes are discussed in four parts – rat and mouse models, dietary induction, and selective breeding. Models are assessed regarding metabolic disturbances, the condition of the pancreas, long-term complications, and research benefits.

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Background: Atherosclerotic complications are one the most common causes of death in patients with type 2 diabetes mellitus. Epidemiological data indicate that the consumption of omega-3 unsaturated fatty acids (O3FA) leads to a reduction in cardiovascular disorders. The metabolic effect of this substance in patients with type 2 diabetes is still a matter of debate, however. The aim of this study was to assess the metabolic effect of O3FA in Iranian diabetic patients.
Methods: 50 diabetic patients (20 men and 30 women mean age 49±7.3 years) were randomly allocated to either the intervention (diet + fish oil containing O3FA) or the control group (diet alone). The lipid and glucose levels, blood pressure, and weight of each patient were measured at the beginning of the study. The duration of the study was 3 months. The aforementioned parameters were re-assessed at the end of the study.
Results: O3FA consumption was associated with a significant reduction in serum triglyceride levels (p<0.001). Reductions in weight, fasting blood sugar, and glycosylated haemoglobin were noted in the intervention group but were not statistically significant. No changes occurred in total cholesterol, HDL, and LDL levels. The dosage of oral hypoglycaemic agents was unchanged in both groups throughout the study.
Conclusion: O3FA may be recommended for the management of hypertriglyceridaemia.

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Background: The non-enzymatic glycosylation (NEG) of proteins in diabetes damages both the structure and function of these proteins. In vivo and in vitro studies have shown that NEG of proteins and advanced glycosylation end-products (AGE) contribute to the pathogenesis of both macrovascular, such as atherosclerosis, and microvascular complications, such as retinopathy and nephropathy, in diabetes.
Methods: We studied the electrophoretic mobility, fluorescence at isoelectric pH, and time-dependent AGE formation of glycosylated albumin. For the first time, we have used isoelectric focusing to study serum glycosylated albumin in diabetic patients and healthy controls. Results: After 10 weeks incubation with glucose, the electrophoretic mobility of glycosylated albumin increased 21.3% compared with normal albumin. The isoelectric pH of albumin decreased from 4.6 on day 1 to 4.1 on day 7. The increase in electrophoretic mobility was accompanied by the drop in pH during the first week of incubation. These changes correlated well with those observed by fluorescence. The glucose content of the albumin samples decreased during the first week of incubation, but gradually increased thereafter. Fluorescence readings agreed with these observations. Using isoelectric focusing, there was a significant difference between the serum albumin of diabetic and normal individuals (p<0.001).
Conclusion: Increased electrophoretic mobility during the first week with a simultaneous decline in isoelectric pH shows that AGE formation begins after the first week. The reduction in glucose concentration during the first week and its subsequent increase during the second week may be attributed to the formation and hydrolysis of AGE. This method may be used to determine the stability or progress of diabetes.

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Background: Diabetes mellitus, the most common metabolic disorder of childhood, has important physical and emotional complications this urges the role of patient education and self-monitoring. Diabetes is costly since patients have to do several lab tests and spend a lot on treatment.
Methods: 150 patients with IDDM entered this cross-sectional study. The metabolic control and degree to which these patients were utilizing available facilities were determined and compared with same surveys from Germany, France, USA, Australia, and Saudi Arabia.
Results: 91.3% of patients had no glucometer thus were unable to do self-monitoring. HbA1C had been regularly determined in only 8.66%. Insulin therapy was improper or inadequate in 59.1%. The quality of metabolic control was significantly poorer than the other mentioned nations (P< 0.001).
Conclusion: The study advocates educational programs for diabetics. Complete insurance coverage and free weekly lab tests are also suggested.

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Background: The American Diabetes Association in 1997 switched its recommendations regarding the screening of pregnant women from universal to risk factor-based screening. The ADA specifically recommended that screening is not cost-beneficial in women under the age of 25, with a normal weight and negative family history of diabetes.
Methods: 910 pregnant women attending the diabetes clinic at Bushehr University of Medical Sciences were screening for gestational diabetes using a 50-gram glucose challenge test. All the women were 24-28 weeks pregnant at the time of testing. Women with a post-load blood glucose of ≥140mg/dl were referred for a 3-hour oral glucose tolerance test. The presence of ADA risk factors was recorded, as was the absence of all three risk factors, and compared with the results of 50-gram GCT. We evaluated the predictive value of different combinations of risk factors relative to the results of screening.
Results: 66 women (6.9%) had a positive screening test, with 16 (1.75%) eventually diagnosed with GDM based on OGTT results. GCT was negative in 616 (95.3%) women, who had at least one of the three risk factors – age >25 years, BMI ≥27kg/m2, or a positive family history of diabetes – and in 231 (27.3%) women who had none of these risk factors [odds ratio = 70.3, 95%-CI = 2.23-22.21 p<0.0001].
Conclusion: Selective screening of pregnant women will detect most cases of gestational diabetes where resources to implement universal screening are limited. The most important factors in selecting screening candidates are age, body mass index, and family history of diabetes mellitus.