مجله دیابت و متابولیسم ایران
سال دوم شماره 1 (پیاپی 3، پائیز و زمستان 1381)

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.

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. 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. 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. O3FA may be recommended for the management of hypertriglyceridaemia.

To compare the effect on insulin absorption intra-nasally of Acanthophyllum squarrosum (ASQ) compared with Acanthophyllum saponaria (ASA) and sodium cholate (NAC), which have proven pro-absorptive effects. The formulation used in this study contained 2IU insulin (per rat), 1% carboxymethylcellulose (CMC) and a pro-absorptive agent at the same concentration. We assessed the hypoglycaemic effect of each formulation in 5 rats in the fasting state. There was no significant difference in the pro-absorptive effects of ASQ, ASA, and NAC. Blood glucose levels 2 hours after administration of insulin, given as a percentage of baseline glucose concentration, were as follows for the three formulations used: ASQ: 36.78±11.06%, ASA: 27.46±2.39%, and NAC: 39.94±14.93%. Acanthophyllum squarrosum has a significant pro-absorptive effect, comparable to that to Acanthophyllum saponaria.

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. 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. 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). 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.

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.

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.

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).

The study advocates educational programs for diabetics. Complete insurance coverage and free weekly lab tests are also suggested.

Cardiac X Syndrome is the occurrence of angina pectoris in spite of a normal coronary angiogram, probably due to a disorder of the cardiac sensory nervous system (pain perception). The insulin resistance (metabolic X) syndrome is an important determinant of coronary artery disease. There is a dearth of research on the association between insulin resistance and cardiac X syndrome. We compared the hormonal status of three groups of postmenopausal women: those with cardiac X syndrome, those with coronary artery disease, and healthy controls. 149 postmenopausal women (age range 48-58 years), matched for duration of menopause, were recruited for this study. Gonadotrophin and fasting insulin levels as well as blood pressure and body mass index were measured in all three groups. LH, FSH, oestradiol and progesterone levels were similar in all three groups. Women in the first two groups (that is, those with angina pectoris regardless of the result of coronary angiography) had a significantly higher BMI than controls. Fasting insulin levels were significantly higher in the first two groups compared with controls (p<0.01). There was no difference in fasting insulin level between the normal and abnormal angiography groups. There was no significant correlation between fasting insulin and any of the other variables, even though the association between fasting insulin and BMI in the abnormal angiography-confirmed CAD group very nearly approached statistical significance (p=0.059). Women with angina pectoris, regardless of the outcome of coronary angiography, have hyperinsulinism and a higher BMI than controls. It seems that hyperinsulinism is the fundamental mechanism by which both the cardiac X and metabolic X syndromes occur. Further research is needed to elucidate this matter.

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. 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. 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]. 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.

Diabetes is a hidden epidemic and the most common metabolic disorder in the world. Immune dysfunction (cellular and humoural) is one of the consequences of diabetes, including defects of phagocyte function, notably in chemotaxis, phagocytosis, and killing. Results of studies on phagocyte respiratory burst activity, however, have been contradictory. We studied the respiratory burst of peripheral blood neutrophils and monocytes separately in response to formyl-met-leu-phe (fmlp) and phorbol-12,13-myristate acetate (PMA). 36 patients with type 2 diabetes (mean age 53±7 years) and 20 healthy controls (mean age 50±5 years) each provided a 15ml blood sample. Peripheral blood neutrophils and monocytes were separated and purified (>95%) using specific density gradients and short-term culture. We then separately assessed respiratory burst activity in response to fmlp and PMA by the semi-quantitative nitroblue tetrazolium (NBT) test. Following stimulation with PMA, diabetic neutrophils showed reduced respiratory burst activity compared with normal neutrophils (p=0.097). Following stimulation with fmlp, too, diabetic neutrophils showed reduced respiratory burst activity compared with normal neutrophils, which this time was statistically significant (p=0.027). There was no difference between diabetic and normal subjects with regards to monocyte response to either fmlp or PMA. It appears that the diminished response and reduced effectiveness of the phagocyte system in people with diabetes can facilitate the onset, exacerbation, and persistence of infection.

There are disputed reports of the beneficial effects of magnetic fields on glucose homeostasis. Continuing from our previous work, we studied the effect of a constant magnetic field on blood glucose and weight gain in laboratory mice. 28 young, female bALB/c mice were randomly allocated into four groups A, B, C and D. Group A were placed in a constant magnetic field for 20 days, group B for 20 days in a placebo field, group C for 10 days in a constant magnetic field, after which the field was removed, and group D for 10 days in a placebo field, which was then removed the remaining 10 days of the study. The induction force of the magnetic field was 500 gauss, and was generated by two natural magnet bars. Placebo fields were created by two identical looking bars of granite. The mice were weighed daily and had their blood glucose measured at the end of the 20-day study. Weight gain was similar in the four groups. Blood glucose was significantly lower in group C mice than in groups B and D mice. No other significant difference in blood glucose between the groups was detected. Even though blood glucose remained unchanged whilst mice are inside a magnetic field, the blood glucose of mice 10 days after field removal is lower than in mice that had never been inside a magnetic field.

We estimated the prevalence of angina pectoris (AP) and myocardial infarction (MI) in the hyperlipidaemic population of Bushehr using the ROSE questionnaire and ECG changes using the Minnesota code. 1036 residents of Bushehr (in southern Iran), aged 30-64 years, were enrolled as part of a 2-year cross-sectional prevalence study of diabetes mellitus and other risk factors for coronary heart disease. All participants completed a ROSE questionnaire and underwent 12-lead electrocardiography. ECG strips were interpreted according to the Minnesota code. The criteria for diagnosing AP was grade 1 or 2 on the angina pectoris diagnostic scale, and for MI, code 1.1 of the Minnesota code or a history of myocardial infarction. The crude prevalence of hypercholesterolaemia was 47.6%, and its age-adjusted prevalence 50.3% in women and 43.9% in men. Mean serum cholesterol was 204.2±49.5mg/dl in women and 195.0±46.1 in men (p=0.003). The prevalence of AP was 4.9%, which, after adjustment for age, came to 5.6% in men and 4.6% in women. The prevalence of AP was 6.3% in subjects with high cholesterol and 3.6% in subjects with normal cholesterol levels (p<0.05). There was a strong association between AP and hypercholesterolaemia in men (p<0.0005). The crude prevalence of MI was 4.1% in subjects with hypercholesterolaemia and 0.9% in subjects with normal cholesterol (p<0.05). In multivariate analysis, MI was correlated with hypercholesterolaemia in both sexes (p<0.05). Similarly, MI in both men and women was associated with diabetes, and in men alone with hypertension (p<0.05). It is imperative to reduce the average cholesterol level of the population of Bushehr in order to decrease the incidence of AP and, ultimately, MI. Interventions to improve people s lifestyle are of one of the effective measures that may be used in this regard.