Real world use of tirzepatide in the treatment of type 2 diabetes in an Arab population.

AIM: Tirzepatide is a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) dual receptor agonist (RA) that reduces glycated haemoglobin (HbA1c) and weight in patients with type 2 diabetes. We assessed the effectiveness of tirzepatide in real-world use in an Arab population. METHODS: Review of clinical data from a specialist outpatient diabetes centre; study time points and outcome measures were pre-specified. RESULTS: Tirzepatide was initiated in 8945 patients between 24 October 2022 and 31 December 2023. Of these, 3686 individuals reached 40 weeks of follow-up. At initiation, the mean ± SD age was 54.1 ± 11.5 years, body mass index 34.6 ± 6.0 kg/m2 and HbA1c 7.3 ± 1.5% (56 ± 17 mmol/mol); 2296 (62%) were switched to tirzepatide from another GLP-RA and 317 (8.6%) reported previous bariatric surgery. The maximum dose dispensed was ≥12.5 mg/week in 1087, 7.5-10.0 mg/week in 1688 and 2.5-5.0 mg/week in 911. The mean 40-week reduction in HbA1c was 0.6 ± 1.2% (8 ± 13 mmol/mol) and the reduction in weight was 4.5 ± 6.9 kg (4.8 ± 7.3%). GLP-RA-naïve patients experienced a significantly greater reduction in HbA1c [1.0 ± 1.3% (11 ± 14 mmol/mol) versus 0.5 ± 1.2% (6 ± 13 mmol/mol), p < .0001] and weight (7.2 ± 8.6 vs. 4.2 ± 6.6 kg, p < .0001) compared with previously exposed individuals. Post-metabolic bariatric surgery patients lost significantly more weight (7.8 ± 9.4 vs. 4.5 ± 7.0 kg, p < .0001). Improvements in blood pressure, lipid profile, and liver transaminases were noted at 40 weeks. Tirzepatide was well tolerated, with 288 (7.8%) of patients discontinuing treatment because of adverse effects, predominantly gastrointestinal. CONCLUSION: In real-world use, tirzepatide significantly reduced HbA1c levels and weight and was well tolerated. Previous GLP-RA use was associated with significantly lesser HbA1c and weight reduction, and previous metabolic bariatric surgery was associated with greater weight loss.

Validation of the new IDF-DAR risk assessment tool for Ramadan fasting in patients with diabetes.

BACKGROUND: A new IDF-DAR (International Diabetes Federation - Diabetes and Ramadan Alliance) risk stratification tool was published in 2021 to better stratify the risk of Ramadan fasting in people with diabetes. METHODS: We performed a prospective, survey-based study before and after Ramadan 1442/2021 to explore the ability of the new IDF-DAR risk stratification tool to predict the probability of fasting and the risk of complications from fasting in people with diabetes. RESULTS: A pre-Ramadan assessment was completed for 659 patients who intended to fast in Ramadan; 647(98.2%) answered the post-Ramadan follow-up questionnaire. Mean age was 53.5 years and 47.9% were females. 603(91.5%) had type 2 diabetes while 56(8.5%) had type 1 diabetes. Using the IDF-DAR risk criteria at the pre-Ramadan assessment, 339(51.4%) were categorized as low-risk (score <3), 173(26.3%) as moderate-risk (score 3.5-6) and 147(22.3%) as high-risk (score >6). 94.3%, 81.1% and 76.9% patients fasted the full 30 days in the low, moderate and high risk groups respectively (p < 0.0001). Any hypoglycaemia was reported in the low, moderate and high risk groups by 6.3%, 21.9% and 35.0% respectively while severe hypoglycaemia was reported by 3(2.1%) patients in the high, 3(1.8%) in the moderate and none(0%) in the low risk groups. Hyperglycaemia (>250 mg/dL) was reported in the low, moderate and high risk groups by 2.7%, 13.0% and 23.8% respectively. CONCLUSION: The new IDF-DAR risk assessment tool appears to reliably predict both the ability to fast during Ramadan as well as the likelihood of getting hypoglycaemia or hyperglycaemia.

Bariatric surgery in the treatment of patients with obesity and type 1 diabetes: A retrospective study of clinical data.

AIM: To evaluate the effectiveness and safety of bariatric surgery in patients with coexisting type 1 diabetes and obesity who choose to undergo bariatric surgery for weight management. MATERIALS AND METHODS: We conducted a retrospective, longitudinal review of the clinical data of patients with type 1 diabetes, followed up at our centre after bariatric surgery had been performed elsewhere. RESULTS: Sixty-one patients were included, of whom 51% were women, and 57 (93%) were Emirati Arab, three (5%) were other Arab, and one (2%) was White in ethnic origin. The mean age at surgery was 31 years. A total of 42 patients (69%) underwent sleeve gastrectomy, 17 (28%) gastric bypass, and two (3%) gastric banding. In 48 patients with complete follow-up data, improvements were observed at 12 months in the median (interquartile range [IQR]) values for body mass index (BMI; 38.5 [34.9-40.9] to 26.1 [24.2-29.6] kg/m2 , P <0.001), glycated haemoglobin concentration (8.6 [7.8-9.2]% to 7.8 [7.2-8.5]%; P <0.001), daily insulin dose (1.0 [0.7-1.2] to 0.8 [0.6-0.9] units/kg/d; P <0.001), systolic blood pressure (127 [116-136] to 116 [110-120] mmHg; P <0.001), total cholesterol: high-density lipoprotein cholesterol ratio (3.4 [2.9-4.3] to 3.0 [2.6-3.5]; P <0.001), and albuminuria. In 32 patients followed up at 3 years, the median (IQR) reduction in BMI was 10.4 (5.9-11.7) kg/m2 , 50% reduced or stopped antihypertensive medication and 58% reduced or stopped lipid-modifying medication. Three patients each reported a single episode of diabetic ketoacidosis; in one case this was due to cessation of insulin treatment. CONCLUSIONS: In our cohort of patients with obesity and type 1 diabetes, bariatric surgery led to significant improvements in weight and cardiometabolic variables, with modest improvements in glycaemia. Few adverse events were reported.

Clinically-Defined Maturity Onset Diabetes of the Young in Omanis: Absence of the common Caucasian gene mutations.

OBJECTIVES: We are seeing a progressive increase in the number of young patients with clinically defined maturity onset diabetes of the young (MODY) having a family history suggestive of a monogenic cause of their disease and no evidence of autoimmune type 1 diabetes mellitus (T1DM). The aim of this study was to determine whether or not mutations in the 3 commonest forms of MODY, hepatic nuclear factor 4α (HNF4α), HNF1α and glucokinase (GK), are a cause of diabetes in young Omanis. METHODS: The study was performed at Sultan Qaboos University Hospital (SQUH), Oman. Twenty young diabetics with a family history suggestive of monogenic inheritance were identified in less than 18 months; the median age of onset of diabetes was 25 years and the median body mass index (BMI) 29 at presentation. Screening for the presence of autoimmune antibodies against pancreatic beta cells islet cell antibody (ICA) and glutamic acid decarboxylase (GAD) was negative. Fourteen of them consented to genetic screening and their blood was sent to Prof. A. Hattersley's Unit at the Peninsular Medical School, Exeter, UK. There, their DNA was screened for known mutations by sequencing exon 1-10 of the GCK and exon 2-10 of the HNF1α and HNF4α genes, the three commonest forms of MODY in Europe. RESULTS: Surprisingly, none of the patients had any of the tested MODY mutations. CONCLUSION: In this small sample of patients with clinically defined MODY, mutations of the three most commonly affected genes occurring in Caucasians were not observed. Either these patients have novel MODY mutations or have inherited a high proportion of the type 2 diabetes mellitus (T2DM) susceptibility genes compounded by excessive insulin resistance due to obesity.

Predictors of avascular necrosis of the hip in Emiratis patients with systemic lupus erythematosus.

Symptomatic avascular necrosis (AVN) of the hip is a known complication of systemic lupus erythematosus (SLE). Data on the prevalence of bone avascular necrosis (AVN) in Arab SLE patients are limited. We conducted a cross-sectional and retrospective case-control study on 126 SLE patients from Dubai to determine prevalence and predictors of symptomatic hip AVN. 8.7% of our lupus cohort demonstrated evidence of symptomatic hip AVN and had longer disease duration, higher cumulative steroid dose, and received cyclophosphamide and mycophenolate mofetil more often than the SLE patients without AVN (controls). Skin manifestations, serositis, lupus nephritis, neuropsychiatric lupus, and sero-positivity for autoantibodies: anti-DNA, Anti-Sm, and antiphospholipid antibodies were higher in patients than controls. Administration of hydroxychloroquine prior to onset of AVN was less frequent in cases than controls. In conclusion, disease activity, steroids, cytotoxic drugs, and antiphospholipid antibodies are important predictors of symptomatic AVN in Emirati patients with SLE, Hydroxychloroquine may play a protective role against developing AVN in Emiratis with SLE. Controlled longitudinal studies are essential to validate these findings.