Diabetes Mellitus - Role of Clinical Laboratory (PDF)

DIABETES MELLITUS: ROLE OF THE CLINICAL LABORATORY by Dr. BASIL, B. (MBBS, FMCPath., IFCAP) Consultant Chemical Pathologist/Metabolic Medicine Physician May 2023...

DIABETES MELLITUS: ROLE OF THE CLINICAL LABORATORY by Dr. BASIL, B. (MBBS, FMCPath., IFCAP) Consultant Chemical Pathologist/Metabolic Medicine Physician May 2023 1  Introduction: The clinical laboratory plays crucial role in the management of Diabetes mellitus (DM). Various biomarkers and laboratory test combinations can be deployed to this effect. The roles of the clinical chemistry laboratory in this regard include: – Screening and diagnosis of DM, – Monitoring of glycemic control (short and long term), – Detection and management of complications of DM. 2  Screening and Diagnosis of DM: Criteria for screening Adults: – Symptomatic hyperglycemia – polyuria, polyphagia, polydipsia, weight loss – 1st degree relative with DM – History of CVD – HTN (>140/90mmHg) – Dyslipidemia – PCOS – Obesity/Overweight (>25kg/m2) – Acanthosis nigricans, fatty liver disease – High risk ethnicity (like Asian Indians) If normal, screen every 3 years or more frequently depending on initial result and risk status 3  Screening and Diagnosis of DM – contd: Criteria for screening children: Overweight child (BMI >85th percentile for age and sex, weight for height >85th percentile, or weight >120% of ideal for height). Plus any TWO of the following: (FRMAS) – Family history of Type 2 DM in first or second-degree relative – Race/Ethnicity – Blacks – Signs of insulin resistance or conditions associated with insulin resistance – Maternal history of diabetes or GDM during the index child’s gestation – Age of 10yrs or at onset of puberty, if puberty occurs at a younger age Frequency – every 3yrs 4  Screening and Diagnosis of DM – contd: Diagnosis of DM involves (2 GFR) Any one of the following: 1. HbA1c ≥ 6.5% (48mmol/mol) 2. FPG ≥ 7.0mmol/L (126mg/dL) 3. Symptoms of hyperglycemia and RBS ≥ 11.1mmol/L (200mg/dL) 4. 2-hr plasma glucose ≥ 11.1mmol/L (200mg/dL) during an OGTT. In the absence of unequivocal hyperglycemia, these criteria should be confirmed by repeating the same test on a different day. Avoid mixing different diagnostic methods when diagnosing DM 5  Monitoring of Glycemic control – Short-term: Blood glucose – Daily fasting glucose – Random/post-prandial glucose – Self-monitoring of blood glucose (SMBG) – Continuous Glucose Monitoring (CGM) Urine glucose 1,5-Anhydroglucitol (1,5-AG) 6  Blood and Urine Glucose: Blood Glucose Urine Glucose Measurements: Measurement: – FPG measurement is a – Identifies severe reliable index of short-term hyperglycemia where renal blood glucose control threshold has been – mean FPG is a helpful exceeded guide to treatment – unreliable due to Variable decisions renal threshold, Low – more important in DM sensitivity and specificity, patients on insulin where influenced by fluid intake, more frequent self-testing drugs, UTI, etc. is required – Negative outcome does not distinguish hypoglycemia, euglycemia and mild or moderate hyperglycemia 7  Self-monitoring and Continuous monitoring of Blood Glucose: Self-monitoring of blood glucose (SMBG) – Needed in people with T1DM and T2DM on insulin – Ideally six times a day: Before meals + Bedtime + Occasional post-meal Continuous Glucose Monitoring (CGM) – Provides insights beyond glucometer – Measures glucose levels in the interstitial fluid – Sensors are implanted and signals relayed on a display for real-time review 8 SMGB vs CGM 9 Continuous Insulin therapy and blood glucose monitoring 10  1,5-Anhydroglucitol (1,5-AG): 1,5-Anhydroglucitol (1,5- Clinical utility of 1,5-AG: AG): – Most useful when day-to-day – The 1-deoxy form of glucose, glucose changes are being a metabolically inert polyol monitored, or – Competes with glucose for – as an adjunct to SMBG to reabsorption into the kidneys confirm stable glycemic – in hyperglycemia (>180 control. mg/dl), even transiently, – Not affected by hypoglycemia urinary loss occurs, and – Better differentiates patients serum levels fall. with extensive glycemic – Tightly associated with rapid excursions who have similar glucose fluctuations and HbA1c values. respond within in 24 hours Limitations of 1,5-AG: – Thus, low 1,5-AG indicates – Unreliable in renal disease hyperglycemia within the and GDM preceding 24 hours 11  Monitoring of Glycemic control – Long Term: HbA1c Glycated Albumin (Fructosamine) Advanced Glycation End-products (AGE) C-peptide Insulin 12  Glycated Haemoglobin (HbA1c): Non-enzymatic attachment of glucose to beta-chain unit of Hb Gold standard for monitoring of DM Reflects average glycemic control over a period of 90 – 120 days – more sensitive to the last 1 month. Does not require any special preparation such as fasting Have strong predictive value for complications of DM – for every 1% decrease in HbA1C, – Microvascular disease decreases by 37% – MI decreases by 14% – Death decreases by 21% Used to confirm the accuracy of patients glucometer, and adequacy of self-monitoring schedule 13  Glycated Haemoglobin (HbA1c) - contd: HbA1c is the measure most commonly studied in clinical trials Must be measured 2-4x/year in DM patients Limitations: – erythrocyte turnover and hemoglobinopathies may yield results that do not correlate with the patient’s clinical situation – Presence of CKD, alcoholism, etc – Does not provide a measure of glycemic variability or hypoglycemia – Increases with age (reasons unclear) – Racial disparities (unclear etiology and significance) – Rapidly evolving T1DM (rare condition) 14 Glycated Haemoglobin (HbA1c) - contd: 15  HbA1c and Plasma Glucose: There is a strong and consistent relationship between HbA1c and Plasma glucose – Average Plasma Glucose (mg/dl) = (HbA1c x 35.6) – 77.3 – Average Plasma Glucose (mmol/L) = (HbA1c x 1.98) – 4.29 16  Glycated Albumin and Fructosamine: Glycated Albumin and fructosamine provide a reliable measure when HbA1c is observed not to be dependable. They reflect glycemic state for a shorter period of 2 - 3wks (as the half-life of albumin is 14 - 21 days), and serve as an index of intermediate-term glycemic control. Fructosamine: – results from covalent attachment of sugar (e.g glucose or fructose) to total serum proteins, primarily albumin, to form ketoamines. – more frequently used to evaluate glycaemic control following recent medication adjustment. Glycated albumin: – reported to be a better marker than HbA1c for monitoring in DM patients with CKD, and those on dialysis 17  Glycated Albumin and Fructosamine – contd: Clinical utility: Limitations: – Monitoring of DM (esp – Underestimates glycemia in fluctuating or poorly the obese controlled), – Affected by changes in the – Prediction of both the synthesis or clearance of microvascular and serum proteins that occur macrovascular complications with acute systemic illnesses – In pregnancy, detection of or liver disease, protein-losing short-term changes in glucose enteropathy or nephrotic levels. syndrome. – May correlate better with – High fructosamine can be due post-load glucose levels to high levels of glycated compared to fasting values, immunoglobulins, specifically and helpful in patients for IgA whom postprandial hyperglycemia is suspected. 18  C-peptide: C-peptide is an important peptide hormone that is cleaved from proinsulin during insulin biosynthesis. Levels reflect the amount of insulin that is being produced by the pancreas. It does not have significant metabolic effects, but has several important roles in assessment of long-term glycemic control in patients with DM including: – Provides an indication of residual beta-cell function in DM patients – Assesses the adequacy of insulin replacement and the need for adjustments in dosages. – Higher levels are associated with lower rates of complications (in T1DM); and better glycemic control and lower rates of CVDs (in T2DM) – Differentiates between DM types – low in T1DM, high or normal in early T2DM 19  Detection and Management of Complications: Acute complications: – DKA – HHS – Hypoglycaemia – Lactic acidosis Chronic complications: – Microvascular: Nephropathy Neuropathy Retinopathy – Macrovascular: Coronary Heart Disease Peripheral Vascular Disease Cerebrovascular disease 20  Acute Complications: ( B L U E S C L A S S G ) Glucose: Lactate: – key test used to diagnose and – To diagnose and monitor monitor DKA, HHS and lactic acidosis hypoglycaemia. Creatinine kinase (CK) level: Electrolytes (with calculated – to monitor the risk of anion gap): rhabdomyolysis, which can – serum sodium – decreased; occur in DKA and HHS. serum potassium – elevated Serum amylase and lipase: (reduced level portend more danger) – to monitor the risk of pancreatitis, which can occur Ketones: in DKA and HHS. – Present in DKA and in home Serum albumin: management of T1DM – to monitor the risk of – β-hydroxybutyrate < 0.60 hypovolemia, which can occur mmol/L = normal; 0.60-1.0 = in patients with DKA and HHS. necessitates more insulin; > 1.0 = warning to seek medical Arterial blood gases care – To access acid-base imbalance 21  Acute Complications – contd: Serum osmolality: – to monitor the risk of hyperosmolar states, such as HHS. – >320mOsm/kg may lead to mental status change. BUN/creatinine: – To monitor for risk of AKI during DKA and HHS Liver enzymes: – AST and ALT; to monitor the risk of liver dysfunction, which can occur in DKA and HHS. Urine dipstick: – To monitor glucose, ketones, SG, pH, etc in DKA and HHS. 22  Chronic Complications: Urine Albumin, ACR and Serum Creatinine level and Microalbumin levels: eGFR: – Target level of Urine Albumin- – Target eGFR: ≥ Creatinine ratio < 30 mg/g in 60mL/min/1.73m2 from a a random spot collection 24hr urine sample collection – Microalbuminuria (>30mg/g – Used (along with ACR and or >30mg/day) – Incipient Cys-C) to monitor onset and Nephropathy. progression of kidney disease – Albuminuria is a marker of in diabetes mellitus patients. greatly increased Serum Cystatin-C: cardiovascular morbidity and – Target level: 0.78-0.86 mg/L mortality – More sensitive marker of – Done once a year in patients renal disease in diabetics with T1DM of at least 5yrs even when eGFR > 60mL/min duration; and once a year in and ACE inhibitors render all patients with T2DM. microalbuminuria detection unreliable. 23  Chronic Complications - contd: Liver enzymes (mostly ALT Lipid Profile (LDL, HDL and elevation): TG): – Most common cause in DM – Dyslipidemia is a strong patients is non-alcoholic liver predisposition for disease (NAFLD). cardiovascular complications – It is characterized by due to its atherogenicity. accumulation of triglycerides – Fasting Target level: LDL: < within the hepatocytes – 2.60 mmol/L; HDL: > 1.15 insulin resistance is thought mmol/L. to play an important role. – Done once a year or 2yearly if – ALT ≤ 250 units/L for > 6 low risk. months requires screening for treatable causes of CLD e.g hsCRP: viral hepatitis, etc. – used to monitor the risk of – Routine monitoring should inflammation and CVDs. commence with start of drug therapy HbA1c: – Used to risk of chronic complications – retinopathy, neuropathy, nephropathy. 24  Conclusion: The clinical laboratory plays a crucial role in the management of DM by providing valuable information for the diagnosis, treatment, and monitoring of the disease. Tests used to manage DM range from simple blood glucose tests to more advanced tests such as insulin and C-peptide assays. These tests have unique roles in assessing glycemic control and predicting the risk of developing chronic complications. By monitoring key biochemical markers and interpreting their results, healthcare professionals can make informed decisions about treatment plans and adjust therapies as needed to optimize glycemic control and prevent complications. This can ultimately lead to improved health outcomes and quality of life for people with DM. 25 THANKS!!! QUESTIONS??? 26