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Disruption of endogenous circadian rhythms has been shown to increase the risk of developing type 2 diabetes, suggesting that circadian genes might play a role in determining disease susceptibility. We present the results of a pilot study investigating the association between type 2 diabetes and selected single nucleotide polymorphisms (SNPs) in/near nine circadian genes. The variants were chosen based on their previously reported association with prostate cancer, a disease that has been suggested to have a genetic link with type 2 diabetes through a number of shared inherited risk determinants. The pilot study was performed using two genetically homogeneous Punjabi cohorts, one resident in the United Kingdom and one indigenous to Pakistan. Subjects with (N = 1732) and without (N = 1780) type 2 diabetes were genotyped for thirteen circadian variants using a competitive allele-specific polymerase chain reaction method. Associations between the SNPs and type 2 diabetes were investigated using logistic regression. The results were also combined with in silico data from other South Asian datasets (SAT2D consortium) and white European cohorts (DIAGRAM+) using meta-analysis. The rs7602358G allele near PER2 was negatively associated with type 2 diabetes in our Punjabi cohorts (combined odds ratio [OR] = 0.75 [0.66-0.86], p = 3.18 × 10(-5)), while the BMAL1 rs11022775T allele was associated with an increased risk of the disease (combined OR = 1.22 [1.07-1.39], p = 0.003). Neither of these associations was replicated in the SAT2D or DIAGRAM+ datasets, however. Meta-analysis of all the cohorts identified disease associations with two variants, rs2292912 in CRY2 and rs12315175 near CRY1, although statistical significance was nominal (combined OR = 1.05 [1.01-1.08], p = 0.008 and OR = 0.95 [0.91-0.99], p = 0.015 respectively). None of the selected circadian gene variants was associated with type 2 diabetes with study-wide significance after meta-analysis. The nominal association observed with the CRY2 SNP, however, complements previous findings and confirms a role for this locus in disease susceptibility.

Fasting the Holy month of Ramadan constitutes one of the five pillars of the Muslim faith. Although there is some evidence that intermittent fasting during Ramadan may be of benefit in losing weight and cardiometabolic risk factors, there is no strong evidence these benefits apply to people with diabetes. The American Diabetes Association/European Association for the Study of Diabetes consensus recommendations emphasize the importance of patient factors and comorbidities when choosing diabetes medications including the presence of comorbidities, atherosclerotic cardiovascular disease, heart failure, chronic kidney disease, hypoglycemia risk, weight issues and costs. Structured education and pre-Ramadan counseing are key components to successful management of patients with diabetes. These should cover important aspects like glycemic targets, self-monitoring of blood glucose, diet, physical activity including Taraweeh prayers, medication and dose adjustment, side effects and when to break the fast. The decision cycle adapted for the specific situation of Ramadan provides an aid for such an assessment. Children with type 1 diabetes should strongly be advised not to fast due to the high risk of acute complications such as hypoglycemia and probably diabetic ketoacidosis (DKA), although there is very little evidence that DKA is increased in Ramadan. Pregnant women with diabetes or gestational diabetes should be advised to avoid fasting because of possible negative maternal and fetal outcomes. Hypoglycemia is a common concern during Ramadan fasting. To prevent hypoglycemic and hyperglycemic events, we recommend the adoption of diabetes self-management education and support principles. The use of the emerging technology and continuous glucose monitoring during Ramadan could help to recognize hypoglycemic and hyperglycemic complications related to omission and/or medication adjustment during fasting; however, the cost represents a significant barrier.

The Meta-Analysis of Glucose and Insulin related traits Consortium (MAGIC) recently identified 16 loci robustly associated with fasting glucose, some of which were also associated with type 2 diabetes. The purpose of our study was to explore the role of these variants in South Asian populations of Punjabi ancestry, originating predominantly from the District of Mirpur, Pakistan. Sixteen single nucleotide polymorphisms (SNPs) were genotyped in 1678 subjects with type 2 diabetes and 1584 normoglycaemic controls from two Punjabi populations; one resident in the UK and one indigenous to the District of Mirpur. In the normoglycaemic controls investigated for fasting glucose associations, 12 of 16 SNPs displayed β values with the same direction of effect as that seen in European studies, although only the SLC30A8 rs11558471 SNP was nominally associated with fasting glucose (β = 0.063 [95% CI: 0.013, 0.113] p = 0.015). Of interest, the MTNR1B rs10830963 SNP displayed a negative β value for fasting glucose in our study; this effect size was significantly lower than that seen in Europeans (p = 1.29×10(-4)). In addition to previously reported type 2 diabetes risk variants in TCF7L2 and SLC30A8, SNPs in ADCY5 (rs11708067) and GLIS3 (rs7034200) displayed evidence for association with type 2 diabetes, with odds ratios of 1.23 (95% CI: 1.09, 1.39; p = 9.1×10(-4)) and 1.16 (95% CI: 1.05, 1.29; p = 3.49×10(-3)) respectively. Although only the SLC30A8 rs11558471 SNP was nominally associated with fasting glucose in our study, the finding that 12 out of 16 SNPs displayed a direction of effect consistent with European studies suggests that a number of these variants may contribute to fasting glucose variation in individuals of South Asian ancestry. We also provide evidence for the first time in South Asians that alleles of SNPs in GLIS3 and ADCY5 may confer risk of type 2 diabetes.

Objective. To explore the impact of maternal body weight on maternal nutrition and micronutrient status in early pregnancy and potential impact on metabolic status in newborns. Methodology. The EU FP7 project GIFTS was conducted from Jan 2012 to May 2014. Demographic details and anthropometric measurements of women in the first trimester of pregnancy were obtained. Blood samples were collected for OGTT, insulin, lipid profile, serum folate, ferritin, vitamin D, vitamin B12, and red cell folate. Newborn anthropometric characteristics were observed. Cord blood samples were collected after delivery for glucose, insulin, and lipid profile of newborns. Results. A total of 301 pregnant mothers, 108 overweight, 63 underweight, and 130 normal weight were included. Prevalence of vitamin D deficiency (<30 ng/mL) and low vitamin B12 (<190 ng/l) were high, 44% and 42%, respectively, in the first trimester. Anemic women (due to B12 or iron deficiency) were 79%, while 72% had low ferritin levels. Gestational diabetes was 16%. Differences were observed between underweight and overweight mothers (P<0.05) for fasting blood glucose, insulin levels, and serum ferritin were observed. No significant difference was observed between vitamin D, serum B12, and red cell folate levels. Conclusion. Prevalence of multiple micronutrient deficiencies was common among Pakistani women during early pregnancy despite the nonvegetarian diet that has important implications for pregnancy care in Pakistan and potentially in expatriate communities living abroad. This trial is registered with ISRCTN number 83599025.

Dr Sania Nishtar is the ideal person to lead WHO and we urge the world's 194 health ministers to elect her as the next Director-General (DG) in the coming World Health Assembly. Every health minister at the World Health Assembly will be aware of the wide and deep challenges facing WHO and global public health, and will be cognisant of the need to find the best leader.

Pakistan is a developing country with limited resources and diverse socio-economic standards. Pakistan has high prevalence of diabetes and its complications, which is a great challenge to the existing health care system. National action plans for control of diabetes have been developed and initiatives have been taken but not at an ideal pace. First National Practice Guidelines for Pakistan were published in 1999. It was very helpful in standardizing the management of Type-2 diabetes. In view of important developments in the field of diabetes during the recent years, it was felt that 1999 National Clinical Practice Guidelines edited, should be revised. Also with rapidly increasing number of diabetic patients and the escalating burden on health economy, it is essential to develop a primary to secondary / tertiary care referral system. These guidelines are developed after an extensive research and cover many aspects of diabetes management. This special communication is an extract of a PROMPT document that has already been published as a Supplement in Pakistan Journal of Medical Sciences in 2017. We hope that these guidelines will help in improving the diabetes care in Pakistan.

To assess the effect of angiotensin converting enzyme inhibition on glomerular filtration rate (GFR) in normotensive patient with type 1 diabetes. A two year non-placebo control prospective study was conducted after ethical approval at Diabetes Centre of Diabetic Association of Pakistan, a WHO collaborating centre in Karachi, Pakistan. All patients with type 1 diabetes visited the out-patients department from August 2009 till July 2011 and those who fulfilled the inclusion criteria were invited to participate. A total of 121 people aged ≥18 years and ≥ 5 years of diabetes were included. Pregnant and lactating woman and those aged <18 years were excluded. GFR was calculated by using CKD-EPI formula (eGFR) at baseline and after two year. On the basis of estimated GFR, patients at baseline were divided according to KDIGO classification of chronic kidney diseases into, hyperfiltration (eGFR ≥ 100 ml/min) and normal filtration group (eGFR < 100 ml/min). All subjects in hyperfiltration group received ACE inhibitor (treatment group) while patients with normal filtration did not receive ACE inhibitor (control group). Fifty two patients (43%) were in the treatment and sixty nine (57%) were in the control group. At baseline eGFR, systolic and diastolic blood pressures between groups were non-significantly different. After two years, compared to baseline, eGFR of the treatment group declined and the control group increased significantly. No significant difference in systolic while diastolic blood pressure of the treatment group increased significantly after two years compared to baseline. In contrast both systolic and diastolic blood pressure of control group increased significantly after two years compared to their baseline values. Present study demonstrated that initiation of ACEI in hyperfiltration stage declined GFR and keep blood pressure within normal range.

John Chambers and colleagues report a genome-wide association study for type 2 diabetes in individuals of south Asian ancestry. They identify six loci newly associated with type 2 diabetes. We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10 −4 for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci ( GRB14 , ST6GAL1 , VPS26A , HMG20A , AP3S2 and HNF4A ) newly associated with T2D ( P = 4.1 × 10 −8 to P = 1.9 × 10 −11 ). SNPs at GRB14 were also associated with insulin sensitivity ( P = 5.0 × 10 −4 ), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function ( P = 0.02 and P = 0.001, respectively). Our findings provide additional insight into mechanisms underlying T2D and show the potential for new discovery from genetic association studies in South Asians, a population with increased susceptibility to T2D.

Hajj is one of the five pillars of Islam and is a must-do for all adult Muslims once in their life provided they are able to do it. Considering the 8.8% global prevalence of diabetes, coupled with the number of Muslims performing Hajj (~2.5 million adult Muslims), it could be estimated that Muslims with diabetes performing Hajj may exceed 220 000 per year. According to Islamic rules, Hajj should not cause severe difficulties for Muslims. The Holy Qur’an specifically exempts from this duty Muslims who are unable physically or financially if it might lead to harmful consequences for the individual. This should be applicable to subjects with diabetes considering its severe and chronic complications. During the Hajj, diet, amount of fluid intake and physical activity may be altered significantly. This exemption from the duty is usually not considered a simple permission; Muhammad the Prophet of Islam mentioned, ‘God likes his permission to be fulfilled, as he likes his will to be executed’. However, most Muslims with diabetes prefer to do the Hajj duty, and this may cause major medical challenges for Muslims with diabetes and their healthcare providers. So it is very important that healthcare providers are aware of the possible risks that could happen during the Hajj. People with diabetes may face many health hazards during the Hajj, including but not limited to the ‘killer triad’: hypoglycemia, foot injury and infections. Many precautions are necessary in the prevention and treatment of possible serious complications. Risk stratification, medication adjustments, proper clinical assessment, and education before doing the Hajj are crucial.

With regard to the paper titled “Effect of Intervention in Subjects with High Risk of Diabetes Mellitus in Pakistan” by Hydrie et al. [1], it was stated that the protocol was approved by the Norwegian Research Council. But the statement was made by mistake.