Long-Term Observation of a Man With Severe Obesity and Undiagnosed Monogenic Diabetes Serendipitously Treated With Metabolic Surgery.

A 43-year-old man, with severe obesity (43 kg/m2) and diabetes (presumed as type 2 diabetes [T2D]), underwent vertical sleeve gastrectomy in 2009 and Roux-en-Y gastric bypass in 2013. Recently, whole exome sequencing (conducted to search for monogenic obesity) serendipitously revealed that the individual harbored a heterozygous glucokinase (GCK) variant p.(Arg422Leu) that was bioinformatically strongly predicted to be likely pathogenic. Therefore, he is likely to have concomitant maturity-onset diabetes of the young (MODY) type 2 (GCK-MODY). A retrospective evaluation of the clinical data showed that the subject was diagnosed with T2D (given his severe obesity) in 2005 and was treated with oral antidiabetic monotherapy. His hyperglycemia was mostly mild (HbA1c [hemoglobin] < 8.1%), consistent with that of MODY2, despite severe obesity. After vertical sleeve gastrectomy, complete diabetes remission (HbA1c <6.0% and fasting plasma glucose <5.6 mmol/L without use of antidiabetic medication) was achieved. The percentage of maximum body weight loss attained after surgery was 23.6%. Euglycemia was maintained during the subsequent decade, up to the last follow-up in 2019, without any sign of hypoglycemia. In conclusion, we report a decade-long clinical experience of a man with severe obesity and diabetes likely due to the coexistence of GCK-MODY and T2D, serendipitously treated with metabolic surgery. Interestingly, metabolic surgery was effective and safe for him.

Metabolic Surgery Diabetes Remission (MDR) Score: a New Preoperative Scoring System for Predicting Type 2 Diabetes Remission at 1 Year After Metabolic Surgery in the Singapore Multi-ethnic Asian Setting.

PURPOSE: The utility of available scoring systems for type 2 diabetes (T2D) remission prediction after metabolic surgery has not been defined in a multi-ethnic Asian population like Singapore. We sought to assess the predictive performance of the Asia-developed ABCD scoring system for T2D remission after metabolic surgery, and develop a new algorithm to improve prediction. MATERIALS AND METHODS: We conducted a retrospective analysis of adults with T2D who underwent either Roux-en-Y gastric bypass or sleeve gastrectomy between 2007 and 2018, and followed for 1 year postoperatively (n = 114, mean age 46 ± 9 years, 48.2% men, body mass index 40.1 ± 6.6 kg/m2). The primary outcome was complete T2D remission defined as HbA1c < 6% without the use of anti-diabetic medication at 1 year after surgery. RESULTS: Complete T2D remission was observed in 47.4% of subjects at 1 year post-surgery. Stepwise logistic regression identified preoperative age, T2D duration, HbA1c, and ß-cell function (estimated by the homeostasis model) as predictors of complete T2D remission. Based on these four variables, we constructed a new 10-point scoring system named Metabolic surgery Diabetes Remission (MDR) score. Compared with ABCD, MDR produced fewer misclassifications at the mid-high scores, achieving a predictive accuracy of 71-100% at 6 points and above. In addition, MDR achieved a higher area under the receiver operating characteristic curve than ABCD for the primary outcome (0.79 versus 0.67, P = 0.007). CONCLUSION: MDR may serve as a useful clinical scoring system for predicting short-term T2D remission after metabolic surgery in Singapore's multi-ethnic Asian cohort.

Efficacy of self-monitoring of blood glucose versus retrospective continuous glucose monitoring in improving glycaemic control in diabetic kidney disease patients.

AIMS: Patients with diabetic kidney disease (DKD) on anti-diabetic agents, are at greater risk of glycemic variations, both hypoglycemia and hyperglycemia. We aimed to compare glycemic control (using HbA1c) and hypoglycemia incidence in patients with Stage 3 DKD (eGFR 30-60 mL/min per 1.73 m2 ), receiving retrospective CGM-guided anti-diabetic therapy versus self-monitoring of blood glucose (SMBG) over 3 months. METHODS: Thirty patients with HbA1c >8% were randomized to 6-day retrospective CGM or SMBG. In the CGM group, CGM was worn at the beginning and 6 weeks. HbA1c, assessment of hypoglycaemia events (self-reported and BG < 4 mmol/L from CGM/SMBG data) and medication adjustment were performed at baseline and 3 months. All patients received education on hypoglycaemia avoidance. RESULTS: Fourteen patients were allocated to CGM and 16 to SMBG. Mean (±SD) eGFR was 42.9 ± 10.3 mL/min. Majority (86.7%) of patients had diabetes duration >10 years and on insulin therapy (90%). HbA1c improved significantly from baseline 9.9 ± 1.2 to 9.0 ± 1.5% (P < 0.001) at 3 months, with no difference between CGM (9.8 ± 1.2 to 8.8 ± 1.8%, P = 0.009) or SMBG (9.9 ± 1.3 to 9.1 ± 1.1%, P = 0.007) groups (P = 0.869 between groups). In the CGM group, percentage duration in hyperglycaemia (BG > 10 mmol/L) reduced from baseline 65.4 ± 22.4% to 54.6 ± 23.6% (P = 0.033) at 6 weeks, with a non-significant rise in percentage duration in hypoglycaemia from 1.2 ± 2.2% to 4.0 ± 7.0% (P = 0.176). There was no difference in self-reported and documented hypoglycaemia events. CONCLUSION: In a pilot study of DKD patients, short-term episodic use of CGM reduced time spent in hyperglycaemia range without significantly increasing time-exposure to hypoglycaemia. However, both CGM and SMBG were equally effective in improving glycaemic control.

Acetyl-keto-ß-boswellic acid induces lipolysis in mature adipocytes.

Recently, it was reported that naturally occurring pentacyclic triterpenoids such as ursolic acid have anti-adiposity property. We studied if acetyl-keto-ß-boswellic acid (AKBA), an established anti-inflammation and anti-cancer pentacyclic triterpenoid which has similar chemical structure to ursolic acid, may modulate adipocyte phenotype. 3T3-L1 murine adipocytes and human subcutaneous adipocytes were treated with AKBA in different concentrations in vitro. AKBA triggered significant lipolysis in 3T3-L1 adipocytes as shown by reduced neutral lipids in cytosol and increased free fatty acids in culture medium. Increased lipolysis by AKBA was accompanied by up-regulation of lipolytic enzymes, adipocyte triglyceride lipase (ATGL) and hormone sensitive lipase (HSL), and a decreased expression of lipid droplet stability regulator perilipin. In addition, AKBA treatment reduced phenotypic markers of mature adipocyte aP2, adiponectin and glut-4 in mature adipocytes. Further studies revealed that AKBA down-regulated PPAR-γ and C/EBP-α expression in a dose and temporal dependent manner in mature adipocytes. In human adipocytes, AKBA likewise mobilized lipolysis accompanied by down-regulation of PPAR-γ2 expression and loss of phenotypic markers of mature adipocytes.