Practice points from latest diabetes CPG

MIMS Doctor summarizes key practice points presented by an expert panel during the CPG Rapid Fire Sessions following the launch of the 6^th edition of the Clinical Practice Guidelines for the Management of Type 2 Diabetes Mellitus (T2DM) earlier this year.

Prevention of T2DM among people with prediabetes
Professor Dato’ Dr Mafauzy Mohamed, Professor of Medicine and Senior Consultant Endocrinologist, Hospital Universiti Sains Malaysia

· Prediabetes is defined as the presence of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), or HbA_1c of 5.6–6.2%.

· Sustained weight loss of 7–10 percent from the initial body weight within 6 months of starting interventions has been shown to prevent T2DM. Strategies for the prevention of T2DM include lifestyle intervention, bariatric surgery and pharmacological agents. [J Acad Nutr Diet 2016;116:129–147; J Am Diet Assoc 2007;107:1755–1767]

· Lifestyle intervention comprises a combination of diet and physical activity. Diet should ideally include plant-based foods, wholegrain, limited red and processed meats and no sugar, and restricted to 1200-1500 kcal/day for women and 1500-1800 kcal/day for men. Physical activity for >150 mins per week of moderate-vigorous intensity is recommended. The use of device-based technology-assisted programmes can assist and motivate people in adhering to diet and physical activity. [J Acad Nutr Diet 2016;116:129–147; J Am Diet Assoc 2007;107:1755–1767]

· Bariatric surgery—laparoscopic gastric bypass, sleeve gastrectomy and adjustable gastric band—is recommended for weight reduction among patients with BMI≥32 kg/m². [Diabetes Obes Metab 2014;16:719–727; Singapore Med J 2018;59:472–475]

· In addition to lifestyle interventions, selected patients may be given pharmacological agents such as metformin, liraglutide 3 mg/day, alpha glucosidase inhibitors, pioglitazone, and orlistat, to prevent or delay the development of T2DM. [BMJ Open 2017;7:e013802; Cochrane Database Syst Rev 2017;5:Cd012204]

· Metformin is the only drug that has also been approved for the treatment of prediabetes to prevent T2DM among very high-risk patients. (Table 1) [Diabetes Care 2019;42(Suppl 1):S29–S33; N Engl J Med 2002;346:393–403; Diabetologia 2006;49:289–297; BMJ 2012;345:e4624]

Monitoring glucose levels using technology
Dr Foo Siew Hui, Senior Consultant Endocrinologist and Head of Endocrine Unit, Hospital Selayang

· Continuous glucose monitoring (CGM) can be performed using a subcutaneously inserted sensor to measure interstitial glucose levels, which correlate closely with plasma glucose. It can be broadly classified into retrospective and real-time, and measured every 5–15 minutes. It is indicated for patients who require intensive glucose control, those who have unrecognized hypo-/ hyperglycaemia or discrepant HbA_1c with self-monitoring of blood glucose (SMBG), or are at high risk of severe hypoglycaemia.

· Retrospective/ professional CGM measures glucose levels every 5 minutes for 24 hours to provide 288 sensor glucose (SG) readings a day, time in range (TIR) for target glucose range, hypoglycaemia and hyperglycaemia, and estimated HbA_1c based on the SG readings.

· Real-time/ personal/ flash CGM, where patients use a device to intermittently scan the sensor to obtain glucose level readings on an on-demand basis, does not need to be calibrated with capillary blood glucose. The sensor life span varies between 6 and 90 days. Some can be integrated into an insulin pump and provide average glucose levels, TIR, percentage of hyperglycaemia readings, and number and average duration of hypoglycaemia events.

· However, ingestion of certain substances like paracetamol may affect the accuracy of the reading for CGM. CGM devices should be removed when patients must undergo MRI, X-ray or deep-sea diving.

· A single-page standardized CGM report provides an overall view of patient’s glycaemic profile and glucose variability which can be shared with healthcare providers (HCPs) and patients for improved glycaemic control. An international consensus of TIR has recommended most patients achieve TIR >70 percent while high-risk or elderly patients can aim for TIR of 50 percent. [Diabetes Care 2019;42:1593–1603]

· Studies have shown that TIR of 70 percent correlates with HbA_1c of about 7%, and an improvement of 10 percent in TIR is associated with 0.6% improvement in HbA_1c. [J Diabetes Sci Technol 2019;13:614–626]

· When using CGM, patients are likely to be motivated to adhere to therapeutic lifestyle changes. However, CGM is costly and may be less accurate especially when glucose levels change rapidly; also, patients and HCPs need to be trained for proper use and interpretation of the report.

· Diabetes self-management may be enhanced with mobile applications, but more evidence is required on accuracy, data security, accessibility, and sustainability.

The link between nonalcoholic fatty liver disease and T2DM
Professor Dr Chan Wah-Kheong, Consultant Gastroenterologist and Hepatologist, Universiti Malaya

· Nonalcoholic fatty liver disease (NAFLD)—characterized by excess accumulation of fat in the liver—is common among patients with T2DM. Most cases are linked to obesity and generally considered as the liver manifestation of the metabolic syndrome. [J Gastroenterol Hepatol 2018;33:70–85]

· Experts have proposed the term metabolic dysfunction-associated fatty liver disease (MAFLD), which is diagnosed when hepatic steatosis, detected by imaging techniques, blood markers or liver histology, is present together with at least two metabolic risk abnormalities such as waist circumference ≥90 cm for men and ≥80 cm for women; BP>130/85 mmHg, triglycerides>1.7 mmol/L, HDL cholesterol<1.0 mmol/L for men/ <1.3 mmol/L for women; prediabetes, HOMA insulin resistance score>2.5, and hs-CRP>2 mg/L. [J Hepatol 2020;73:202–209; Hepatol Int 2020;14:889–919]

· Nonalcoholic steatohepatitis (NASH) is the more severe form of NAFLD, which is defined histologically by the presence of lobular inflammation and hepatocyte ballooning. Patients with NASH are more likely to develop liver fibrosis and cirrhosis, and hepatocellular carcinoma (HCC). [J Gastroenterol Hepatol 2018;33:70–85]

· NAFLD is extremely common among T2DM patients and is the liver manifestation of the metabolic syndrome. NAFLD and T2DM represent two sides of the same coin.

· The prevalence of NAFLD diagnosed by ultrasound is nearly 50 percent. [J Gastroenterol Hepatol 2013;28:1375–1383] However, a subsequent study where NAFLD was diagnosed based on transient elastography, which is more sensitive than ultrasound, almost three-quarters of patients in the same setting had NAFLD. [J Gastroenterol Hepatol 2019;34:1396–1403]

· T2DM increases the risk of more severe NAFLD, NASH and advanced liver fibrosis (ALF)—the prevalence of ALF diagnosed by liver stiffness measurement (LSM) was >20 percent; among patients who had LSM ≥8 kPa and underwent liver biopsy, 83 percent had NASH, 87 percent had some degree of liver fibrosis, and 36 percent had ALF. [J Gastroenterol Hepatol 2019;34:1396–1403] LSM is a simple and reliable noninvasive test to diagnose liver fibrosis.

· T2DM patients with NAFLD should be assessed using blood tests ie, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and platelet count, and fibrosis score, and when indicated, LSM. For patients with normal ALT and AST levels, the tests can be repeated annually. For those with elevated ALT and AST levels, abdominal ultrasound is recommended to diagnose fatty liver and exclude focal liver lesion along with repeat ALT and AST tests after 3–6 months. It is important to exclude other causes of liver disease such as hepatitis B, hepatitis C, and drug- or alcohol-induced liver injury. Patients with persistently elevated serum ALT and AST levels should be considered for referral to a gastroenterologist/ hepatologist. [CPG Management of T2DM 6^th Edition]

· Serum ALT and AST levels together with platelet count can be used to calculate fibrosis-4 (FIB-4) score, an excellent tool to exclude ALF. Patients with a FIB-4 score <1.3 are at low risk for ALF. FIB-4 scoring can be repeated every 2–3 years. Those with a FIB-4 score ≥1.3 are at intermediate-to-high risk for ALF and should be referred for LSM and can be considered for referral to a gastroenterologist/ hepatologist. [CPG Management of T2DM 6^th Edition; Gastroenterology 2019;156:1264–1281.e4]

· Lifestyle intervention is the mainstay for treatment of NAFLD. Statins should be prescribed for treatment of dyslipidaemia in NAFLD patients, when indicated, to reduce the risk of cardiovascular disease. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and/or sodium-glucose cotransporter-2 inhibitors (SGLT2i) should be considered for the treatment of T2DM in patients with suspected or confirmed NASH and/or ALF. [CPG Management of T2DM 6^th Edition] Weight loss of ≥10 percent through lifestyle intervention over 52 weeks in biopsy-proven NASH patients led to resolution of NASH in 90 percent of patients and improvement of fibrosis in 45 percent of patients. [Gastroenterology 2015;149:367–378]