Although long acting, glibenclamide is frequently given in split doses for type 2 diabetes mellitus. This may discourage compliance. It is thus appropriate to consider dosing it less frequently. We therefore studied glibenclamide effects when used once daily and when used in split doses. Our objective was to assess the feasibility of using once daily dosing as a regimen of choice. We measured plasma glucose, insulin, glibenclamide, lipids, HbAl and body mass index associated with the regimens. We also compared the number of hypoglycemic episodes occurring with them. Thirty type 2 diabetics on multiple daily glibenclamide were enrolled. Their regimens were changed over to once daily. Blood for glucose, insulin, lipids, HbAl and glibenclamide and body weight measurements were determined before and after the crossover period. We found no major difference in the sugar and insulin profiles with the two regimens. Fasting total cholesterol and triglyceride were also similar and so were plasma glibenclamide. The HbAl levels and body mass index and number of minor and major hypoglycemic episodes and hospital admissions for hypoglycemia also did not differ. We conclude that single daily dosing of glibenclamide was equivalent to multiple daily dose regimens. It can be used to an advantage to improve patient's compliance.
Matched MeSH terms: Diabetes Mellitus, Type 2/blood; Diabetes Mellitus, Type 2/drug therapy*
Population studies all over the world have clearly showed that the prevalence of Type 2 diabetes mellitus (DM) is escalating at phenomenal scale and very likely we are heading towards epidemic proportions. In 1985, the estimated population of diabetic individuals in the world was 30 million but by 1995 this figure soared to 135 million. Based on current trends, epidemiologists predict that the population of diabetic individuals will swell up to a staggering 300 million by the year 2025. Almost half of that will be in the Asia Oceania region alone. Dr Hilary King of WHO pointed out that there will be a projected rise of about 42% in developed countries whereas the developing countries will see an escalation to the magnitude of 170% (H. King, R.E. Aubert, W.H. Herman, Global burden of diabetes, 1995-2025: prevalence, numerical estimates and projections, Diabetes Care 21 (1998) 1414-1431; WHO Health Report 1997, WHO Switzerland). There will be a 3-fold rise of the disease in Asia and much of these will be seen in China (40 million) and India (55 million) by virtue of the massive population of these countries. Nevertheless, the other rapidly developing Asian nations like Singapore, Malaysia, Thailand and those making up Indochina will experience the surge. At the same time the prevalence and incidence of diabetes complications will also increase. Based on recent WHO prediction (WHO Newsletter, The global burden of diabetes 1995-2025. World Diabetes 3 (1997) 5-6), it is estimated that by the year 2000 the following figures will be seen:Diabetes complications are major causes of premature death all over the world and most of these are avoidable. DCCT and UKPDS are landmark studies showing strong evidence that major complications can be drastically reduced by maintaining to near normoglycaemic control.
Matched MeSH terms: Diabetes Mellitus, Type 2/epidemiology*; Diabetes Mellitus, Type 2/physiopathology
Diabetes mellitus has been on the rise in Singapore, while Singaporeans are becoming more affluent, our lifestyles are more sedentary and our population is ageing rapidly. The prevalence of diabetes mellitus rose from 2% in 1975 to 4.7% in 1984, 8.6% in 1992 and 9.0% of adults 18-69 years old in 1998. Malay and Indian women and Indian men were at higher risk, with 14.3, 14.9 and 16.7% prevalence rates, respectively. A further 15% of the adult population have impaired glucose tolerance (IGT). Diabetes was a factor in 39.7% of strokes and in 9.3% of all deaths in Singapore, and is the sixth most common cause of death. In the Diabcare Singapore 1998 Study, 91% of participants were diagnosed with Type 2 diabetes, with mean BMI of 25.1+/-4.4 kg/m(2). The incidence of Type 1 diabetes in childhood is 2.46 per 100000 children 0-12 years of age, while Type 2 diabetes in childhood is an emerging problem. The prevalence of obesity (BMI >30 kg/m(2)) among persons aged 18-69 years rose to 6% in 1998, up from 5.1% in 1992. The prevalence of obesity was highest among the Malays (16.2%) followed by the Indians (12.2%) and the Chinese (3.8%). About 12% of schoolchildren are obese. Increased efforts must be made to change lifestyle and eating patterns in our society, reduce childhood obesity and encourage adults to make lifelong sports and exercise part of the Singaporean way of life. Singapore has one of the world's fastest ageing populations, and even now, 32.4% of Singaporeans 60-69 years of age have diabetes. We should consider screening for diabetes in obese schoolchildren and seek to improve quality of care for people with diabetes, including enlisting the aid of community organisations to improve access to diabetes education, monitoring, support and complications screening services.
Matched MeSH terms: Diabetes Mellitus, Type 2/epidemiology
AIMS: To define the prevalence of dyslipidaemia in young diabetic patients in Peninsular Malaysia and the contributory factors of dyslipidaemia in these subjects.
METHODS: This is a cross-sectional study involving 848 young diabetic patients from seven different centres, with representation from the three main ethnic groups. Clinical history and physical examination was done and blood taken for HbA1c, fasting glucose, total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol and triglycerides.
RESULTS: The overall lipids were suboptimal, worse in Type 2 diabetes mellitus (DM) patients compared with Type 1 DM patients. Of the Type 2 patients, 73.2% had total cholesterol > 5.20 mmol/l, 90.9% had LDL-cholesterol > 2.60 mmol/l, 52.6% had HDL-cholesterol < 1.15 mmol/l and 27.3% had serum triglycerides > 2.30 mmol/l. There were ethnic differences in the lipid levels with the Malays having the highest total cholesterol (mean 6.19 mmol/l), and the highest LDL-cholesterol (mean 4.16 mmol/l), while the Chinese had the highest HDL-cholesterol (geometric mean 1.24 mmol/l). Ethnicity was an important determinant of total, LDL- and HDL-cholesterol in Type 2 DM, and LDL- and HDL-cholesterol and triglycerides in Type 1 DM. Glycaemic control was an important determinant of total, LDL-cholesterol and triglycerides in both Type 1 and Type 2 DM. Waist-hip ratio (WHR) was an important determinant of HDL-cholesterol and triglycerides in both types of DM. Gender was an important determinant of HDL-cholesterol in Type 2 DM, but not in Type 1 DM. Socioeconomic factors and diabetes care facilities did not have any effect on the dyslipidaemia.
CONCLUSIONS: The prevalence of dyslipidaemia was high especially in Type 2 DM patients. Ethnicity, glycaemic control, WHR, and gender were important determinants of dyslipidaemia in young diabetic patients. Diabet. Med. 18, 501-508 (2001)
Matched MeSH terms: Diabetes Mellitus, Type 2/blood; Diabetes Mellitus, Type 2/complications
Indo-Asians in the UK are at an increased risk of coronary artery disease (CAD); this may be a reflection of their cardiovascular risk factor profile as well as of a more sedentary lifestyle. We hypothesised that Indo-Asians in Malaysia and the UK may exhibit a similar cardiovascular risk factor and physical activity profile, which would be more adverse compared with caucasians. We studied 70 consecutive Indo-Asian patients admitted to hospitals in Kuala Lumpur, Malaysia (n=42; 35 males; mean age 60.6 years, SD 11.8); and Birmingham, England (n=28; 20 males; mean age 60.8 years, SD 12.9). Both groups of Indo-Asian patients were compared with 20 caucasian patients (13 males; mean age 62.7 years, SD 9.4) admitted with myocardial infarction from Birmingham. There was a higher prevalence of diabetes among Indo-Asians in both countries than among caucasians (p=0.0225). By contrast, caucasians had a higher prevalence of hypercholesterolaemia (p=0.0113), peripheral vascular disease (p=0.0008), regular alcohol consumption (p<0.0001) and family history of CAD (p=0.0041). There were no significant differences in mean age, body mass index or blood pressures. There was a significantly lower leisure activity score (p=0.001) and total physical activity score (p=0.003) among Indo-Asians in both countries than among caucasians. This survey has demonstrated differences in cardiovascular risk factors among Indo-Asian and caucasian patients. The high prevalence of diabetes, as well as the lower physical activity and sedentary lifestyles among Indo-Asians, in both Malaysia and the UK, may in part contribute to the high incidence of CAD in this ethnic group.
Matched MeSH terms: Diabetes Mellitus, Type 2/ethnology
A cross sectional study on Type 2 diabetes patients seeking treatment in the Primary Health Care outpatient clinic of the University Malaya Medical Centre, Kuala Lumpur was undertaken. Two hundred and thirty-three subjects participated. They were asked questions on biodata and dietary intake using face-to-face interview techniques. Dietary intake was assessed using the 24-hour dietary recall. Anthropometric measurements including weight and height were taken and Body Mass Index (BMI) was computed to establish the extent of obesity. Of the 196 subjects, 66.8% were overweight (BMI ≥25 kg/m2) with 15.8% obese (BMI ≥30 kg/m2). The mean BMI of males and females were 25.9±4.3 kg/m2 and 27.2±4.7 kg/m2 respectively. The findings from the dietary survey showed that the mean energy intake of the subjects only achieved about 72% of the Recommended Daily Allowance (RDA) for Malaysia while protein intake of all subjects was adequate. The macronutreint contribution to the total calorie was consistent with the recommendation of the Malaysian Diabetic Association for a healthy diet for diabetes patients. The male subjects were found to meet the RDA requirements for all nutrients while the female subjects did not have sufficient intake of calcium, vitamin A and niacin. No consistent pattern in energy and nutrient intake was observed among different age groups. On the other hand, the Malay subjects seemed to have lower energy and all nutrient intake (except vitamin A and vitamin C) compared to the Chinese and Indian subjects. The Indian subjects seemed to have the highest intake of calcium compared to the others. Advice needs to be given to those who did not have adequate nutrient intake as well as those who need to reduce their weight.
Study site: Primary health care clinic, University Malaya Medical Centre (UMMC)
Metformin Associated Lactic Acidosis (MALA) is a rare, but serious complications of Type 2 diabetes mellitus treatment with a mortality rate of around 50%. It most commonly occurs in the setting of hepatic, cardiac or renal insufficiency. We report the case of an elderly female with MALA and concomitant starvation ketosis in the absence of any known risk factor, who went undiagnosed for a period of at least a month and made a complete recovery in the hospital.
This cross-sectional study compared serum lipoprotein (a) [Lp(a)] concentrations in type 1 and type 2 diabetic subjects and examined the determinants of Lp(a) concentrations in both types of diabetes. Serum Lp(a) was measured in 26 type 1 and 107 type 2 diabetic patients and 126 non-diabetic controls. HbA(1c), fasting lipids and urinary albumin were also assayed. Lp(a) concentrations were higher in both type 1 and type 2 diabetic patients compared with controls (P<0.0001 and P<0.0001, respectively), and were higher in type 1 than type 2 diabetic patients (P<0.05). Waist-hip ratio (WHR) was an independent determinant of Lp(a) concentrations in both type 1 and type 2 diabetes.
Matched MeSH terms: Diabetes Mellitus, Type 2/blood*; Diabetes Mellitus, Type 2/physiopathology
A nonrandomized, non-placebo-controlled clinical trial to evaluate the efficacy of Cogent db (an herbal preparation; Cybele Herbal Laboratories [PVT] Ltd. Kochi, Kerala State, India) as an adjuvant in the treatment of patients with type 2 diabetes was carried out during a 3-month period.
Matched MeSH terms: Diabetes Mellitus, Type 2/blood; Diabetes Mellitus, Type 2/drug therapy*
This study was undertaken to assess the recent data on Malaysian adult body weights and associations of ethnic differences in overweight and obesity with comorbid risk factors, and to examine measures of energy intake, energy expenditure, basal metabolic rate (BMR) and physical activity changes in urban and rural populations of normal weight. Three studies were included (1) a summary of a national health morbidity survey conducted in 1996 on nearly 29 000 adults > or =20 years of age; (2) a study comparing energy intake, BMR and physical activity levels (PALs) in 409 ethnically diverse, healthy adults drawn from a population of 1165 rural and urban subjects 18-60 years of age; and (3) an examination of the prevalence of obesity and comorbid risk factors that predict coronary heart disease and type 2 diabetes in 609 rural Malaysians aged 30-65 years. Overweight and obesity were calculated using body mass index (BMI) measures and World Health Organization (WHO) criteria. Energy intake was assessed using 3-d food records, BMR and PALs were assessed with Douglas bags and activity diaries, while hypertension, hyperlipidaemia and glucose intolerance were specified using standard criteria. The National Health Morbidity Survey data revealed that in adults, 20.7% were overweight and 5.8% obese (0.3% of whom had BMI values of >40.0 kg m(-2)); the prevalence of obesity was clearly greater in women than in men. In women, obesity rates were higher in Indian and Malay women than in Chinese women, while in men the Chinese recorded the highest obesity prevalences followed by the Malay and Indians. Studies on normal healthy subjects indicated that the energy intake of Indians was significantly lower than that of other ethnic groups. In women, Malays recorded a significantly higher energy intake than the other groups. Urban male subjects consumed significantly more energy than their rural counterparts, but this was not the case in women. In both men and women, fat intakes (%) were significantly higher in Chinese and urban subjects. Men were moderately active with the exception of the Dayaks. Chinese women were considerably less active than Chinese men. Chinese and Dayak women were less active than Malay and Indian women. In both men and women, Indians recorded the highest PALs. Hence, current nutrition and health surveys reveal that Malaysians are already affected by western health problems. The escalation of obesity, once thought to be an urban phenomenon, has now spread to the rural population at an alarming rate. As Malaysia proceeds rapidly towards a developed economy status, the health of its population will probably continue to deteriorate. Therefore, a national strategy needs to be developed to tackle both dietary and activity contributors to the excess weight gain of the Malaysian population.
Study name: National Health and Morbidity Survey (NHMS-2006)
Matched MeSH terms: Diabetes Mellitus, Type 2/complications; Diabetes Mellitus, Type 2/epidemiology
This study compared treatment with a prandial glucose regulator (repaglinide) and a sulphonylurea (glibenclamide) in Muslim Type 2 diabetic patients who practice Ramadan fasting. Two hundred and thirty-five patients, previously treated with a sulphonylurea, were randomised to receive either repaglinide (n=116, preprandially three-times daily) or glibenclamide (n=119, preprandially once- or twice-daily) 6 weeks before Ramadan. During Ramadan, patients changed their eating pattern to two meals daily, and the daily dose of repaglinide was redistributed to two preprandial doses. After Ramadan, patients resumed their regular meal pattern and treatment dosage for 4 weeks. During Ramadan, a statistically significant reduction in mean serum fructosamine concentration from baseline was observed in the repaglinide group (-16.9+/-4.9 micromol/l, -3.8%, P<0.05) but not the glibenclamide group (-6.9+/-4.8 micromol/l, -0.8%). Difference in change in HbA(1c) from baseline was not statistically significant between groups. The number of hypoglycaemic events with midday blood glucose <4.5 mmol/l was significantly lower in the repaglinide group (2.8%) than the glibenclamide group (7.9%) (P=0.001). Apart from hypoglycaemia, both treatments were equally well tolerated. Type 2 diabetic Muslims using prandial repaglinide showed a trend towards better glycaemic control and had a lower frequency of hypoglycaemia than patients using glibenclamide during Ramadan.
Matched MeSH terms: Diabetes Mellitus, Type 2/blood; Diabetes Mellitus, Type 2/drug therapy*
The prevalence of diabetes is increasing worldwide. The World Health Organisation has estimated that there will be around 300 million diabetics by 2025. The largest increase will occur in Asia. The prevalence of type 2 diabetes is increasing due to a combination of factors: increasing lifespan, sedentary lifestyle, excessive intake of high energy foods, increasing prevalence of overweight/obese people. The Finnish Diabetes Prevention Study Group has clearly shown that changes in the lifestyle of both overweight men and women with impaired glucose tolerance can reduce the incidence of type 2 diabetes by 58%. This finding was confirmed by the Diabetes Prevention Programme which found that lifestyle intervention in individuals with impaired fasting glucose or impaired glucose tolerance reduced the risk of developing type 2 diabetes by 58%, whereas treatment with metformin reduced the risk of type 2 diabetes by only 31%. Both acarbose and troglitazone have also been shown to reduce the progression to diabetes in individuals who are at high risk of developing type 2 diabetes. Since the cure for diabetes remains some way off our concerted efforts should be directed at prevention of diabetes in order to curb the increasing prevalence of diabetes worldwide. Lifestyle changes are more beneficial than long term drug therapy in the prevention of diabetes and should be actively promoted.
Matched MeSH terms: Diabetes Mellitus, Type 2/drug therapy; Diabetes Mellitus, Type 2/prevention & control*
Two hundred and eleven (211) patients with type 2 diabetes mellitus who were on treatment and monitored for complications at the Outpatient Diabetes Clinic in Hospital Universiti Sains Malaysia, Kubang Kerian between 2001 - 2002 were selected for the study. A structured questionnaire was administered to obtain their medical and family history. Physical examination was performed and fasting venous blood sample was collected for plasma glucose and A1C analysis. Of the total 211 patients, only 4 % were on diet treatment alone, 37 % of them were on mono therapy while 59 % were on combination of therapies. Fasting plasma glucose (FPG) > 7.2 mmol/L and glycated hemoglobin (A1C) levels ≥ 7 % were observed in 60 % and 73 % of type 2 diabetic patients, respectively. Glycated hemoglobin level of 28 % of the subjects were < 7 %; 36 % were between 7 - 9 % and 36 % were more than 9 %. The worst glycaemic control was observed in Malay patients. A1C of Malay and non-Malay subjects were 8.7 ± 2.3 % and 7.7 ± 1.7 %, respectively. Younger patients (age group < 50 years) had significantly higher mean A1C than elderly patients. Duration of diabetes had a clear influence on glycaemic level. Patients with recently diagnosed diabetes (duration of disease < 5 years) had the best glycaemic control. In this study a large proportion of the patients had poor glycaemic control. The variables with significant effects on glycaemic control were ethnicity, age and duration of diabetes mellitus. Better treatment strategies and methods should be used to improve diabetes control and to reduce long-term complications of diabetes.
Study site: Outpatient diabetic clinic, Hospital Universiti Sains Malaysia, Kelantan, Malaysia
The use of Complementary Medicine (CM) amongst diabetic patients attending the Diabetes/Hypertension, Clinic. Out Patient Department, Ipoh Hospital was studied: Forty-three patients were selected by systematic random sampling (1:5) over a one-week period starting 5/12/01. Data were collected by patient interview, from medical records and through a questionnaire. 56% were using CM together with conventional therapy. Most commonly used were herbal therapy, homeopathy and reflexology. The majority took CM daily with a mean duration of 7 years. Over half had subjective relief of pain with increased energy. Patients on CM or conventional therapy both showed poorly controlled FBS levels. There is a need to assess the effect of these therapies on diabetic outcome.
Study site: Diabetes/Hypertension, Clinic. Out Patient Department, Hospital Ipoh, Perak, Malaysia
Matched MeSH terms: Diabetes Mellitus, Type 2/therapy*
Background and purpose: Diabetes mellitus is a strong risk factor for stroke. However, the prognosis in terms of mortality after a stroke is still unclear, especially in diabetic patients. The main purpose of this study was to compare and evaluate the features of stroke in patients having diabetes mellitus with those without diabetes mellitus and to identify factors that influence survival following a stroke.
Subjects and methods: In a prospective hospital-based study consecutive patients with acute ischaemic stroke were enrolled. A single observer, using predefined diagnostic criteria recorded the demographics, risk factors and the type of stroke and deaths that occurred during the in-patient period.
Results: One hundred and sixty-three patients with acute ischaemic stroke were enrolled in the study. Type 2 diabetes mellitus was present in 90 (55.2%) patients. Diabetes was a significant independent predictor of mortality (OR 4.88; 95%CI 1.25-19.1). Among the diabetic patients middle cerebral artery (MCA) territory infarct (OR 34.8, 95%CI 4.5-269.4) and Glasgow coma score (GCS) less than 9 (OR 12.3, 95%CI 3.7-198.1) were independent predictors of mortality.
Conclusions: MCA infarcts and poor conscious level increase the mortality in diabetic patients with stroke. Mortality is also significantly related to a high level of blood glucose at admission.
Ethnic differences exist in patients with diabetes mellitus. Not much is known about such differences in Asian populations. The aim of the study was to determine ethnic differences among Chinese, Malay and Indian patients with type 2 diabetes mellitus in Singapore.
Matched MeSH terms: Diabetes Mellitus, Type 2/diagnosis*; Diabetes Mellitus, Type 2/drug therapy; Diabetes Mellitus, Type 2/ethnology*
Achieving glycaemic goals in diabetics has always been a problem, especially in a developing country with inadequate facilities such as in Sarawak in Malaysia. There are no reported studies on the control of diabetes mellitus in a diabetic clinic in the primary health care setting in Sarawak. This paper describes the profile of 1031 patients treated in Klinik Kesihatan Tanah Puteh Health Centre. The mean age was 59 years, the mean BMI 27 kg/m2. There was a female preponderance and mainly type-2 diabetes. Mean HbA1c was 7.4%. Glycaemic control was optimal in 28% (HbA1c <6.5%), fair in 34% (HbA1c 6.5-7.5%) and poor in 38% (HbA1c >7.5%). Reasonable glycaemic control can be achieved in the primary health care setting in Sarawak.
Study site: Klinik Kesihatan Tanah Puteh, Sarawak, Malaysia
Matched MeSH terms: Diabetes Mellitus, Type 2/blood; Diabetes Mellitus, Type 2/therapy*
To examine a possible association between lipoprotein(a) [Lp(a)] levels and diabetic retinopathy in patients with type 2 diabetes mellitus. 100 type 2 diabetic patients were assessed with the following parameters: age, body mass index, duration of diabetes, blood pressure, fasting plasma glucose, total cholesterol, HDL-cholesterol, triglycerides, blood urea nitrogen, creatinine, Lp(a), and albumin excretion rate (AER). Retinopathy was classified as normal retina (NR), non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR) by an ophthalmologist. The PDR group had higher cholesterol (t=-2.24, p<0.05) and creatinine (z=-2.547, p<0.05) levels than the NPDR group. The PDR group had a higher value of AER (z=-2.439, p<0.01) than the NR group. The possibility of developing diabetic retinopathy after 10 years of diabetes was found to be 6.5 fold high (OR; 6.57, 95% CI 1.74-24.79; p<0.05). The Lp(a) levels were similar in the patients with retinopathy and those without retinopathy. In the study, there was no evidence for a relationship between the serum Lp(a) levels and diabetic retinopathy in type 2 diabetic patients.
Study site: diabetic outpatient clinic at Haydarpasa Numune Education and Research Hospital in Istanbul, Turkey.
Matched MeSH terms: Diabetes Mellitus, Type 2/complications*
We determine the familial aggregation and determinants of post challenge blood glucose (BG) in four ethnic populations. A national health survey was conducted in Malaysia in 1996. 18,372 subjects aged 30 years or older had post challenge BG measurements and another 846 subjects were pre-diagnosed to have diabetes on drug treatment. We imputed the BG of diagnosed diabetics by randomly selecting a value from the BG distribution of undiagnosed diabetics. Covariates of interest include ethnicity, gender, age, urban-rural residence, body mass index (BMI), physical activity, education, and household income. Ethnic and gender differences in mean BG persisted after adjustment for other covariates. Age and BMI were the only two factors with strong, positive and consistent effects on mean BG in all ethnic-sex groups. Family resemblance for BG as measured by intraclass correlation was small and homogenous across all ethnic groups and did not differ from resemblance in BG between spouses. In conclusion, BMI was the only consistent modifiable predictor of BG in all ethnic-sex groups. Environmental factors are probably more important than genetic factors as determinant of BG in the four ethnic populations studied.
Matched MeSH terms: Diabetes Mellitus, Type 2/blood; Diabetes Mellitus, Type 2/diagnosis*; Diabetes Mellitus, Type 2/ethnology
Haemangiopericytoma (HPC) is a rare tumour with a predilection for the central nervous system. Though previously thought to originate from the meninges and ventricular walls, HPC's are currently accepted as distinct mesenchymal neoplasms unrelated to meningiomas. Haemangiopericytomas have been previously reported to be associated with the production of insulin like growth factor II (IGF-II) and hypoglycaemia. A case of a 61-year-old poorly controlled diabetic lady with a rare presentation of an abdominal haemangiopericytoma is discussed. A laparoscopic assisted resection of the massive lobulated tumour arising from the parietal peritoneum with dense attachment to the diaphragm and the liver was performed with an uncomplicated postoperative recovery. Control of the patient's diabetes improved dramatically following surgery and the rare association of hyperglycaemia and HPC, which has not been previously described, is elaborated upon in this report.
Matched MeSH terms: Diabetes Mellitus, Type 2/complications*