Monitoring Diabetes Mellitus PDF

# Monitoring Diabetes Mellitus ## Dr Verena Gounden Consultant Chemical Pathologist Galway University Hospitals ## Overview - Monitoring related to complications - Acute: Diabetic Ketoacidosis - Chronic: Renal, Atherosclerotic/dyslipidaemia - Lab investigations used for monitoring - Self...

# Monitoring Diabetes Mellitus ## Dr Verena Gounden Consultant Chemical Pathologist Galway University Hospitals ## Overview - Monitoring related to complications - Acute: Diabetic Ketoacidosis - Chronic: Renal, Atherosclerotic/dyslipidaemia - Lab investigations used for monitoring - Self monitoring ## Diabetic Ketoacidosis - In about 25% of T1DM patients, their ability to compensate for their insulin deficiency has failed at presentation due to: - delayed presentation - inability to respond to thirst - intercurrent illness - These patients present with a more severe metabolic disturbance known as diabetic ketoacidosis - This is life-threatening condition in which severe insulin deficiency leads to: - Hyperglycaemia (usually >25 mmol/L) - Ketosis (usually > 3 mmol/L) - Metabolic Acidosis - Volume Depletion & Shock - Electrolyte disturbances - Additional symptoms to those described earlier include: - Abdominal pain, nausea, vomiting - Variable effects on mental status from drowsiness with profound lethargy to coma ## Normal Fasting Ketosis - In the fasting state, as plasma glucose levels drop, the pancreas stops producing insulin - Lack of insulin increases lipolysis in adipose tissue with the release of fatty acids into the bloodstream - Fatty acids can be metabolised as an energy source by most tissues (fatty acid β-oxidation) - However, free fatty acids cannot cross the blood brain barrier - Therefore, in the fasting state fatty acids are also oxidised in the liver to 'ketone bodies', acetoacetate & β-hydroxybutyrate, which can be used as an energy source by the brain & other tissues. After 3-4 day fast, ketone bodies provide 30-40% of the body's energy requirements - Acetoacetate can undergo spontaneous decarboxylation to acetone which gives rise to a characteristic fruity odour from breath associated with fasting ## Ketosis in Diabetes - In untreated T1DM, the hormonal milieu is similar to fasting: - severe insulin deficiency can give rise to a ketosis similar to fasting - excessive ketone production can be detected in urine (ketonuria) & blood (ketonemia) - As in fasting, acetone gives rise to a characteristic fruity odour from breath ## Ketoacidosis in Diabetes - Markedly elevated levels of acetoacetate & β-hydroxybutyrate (ketoacids) induce a metabolic acidosis - pH will be low, in severe cases dropping below 7.0 (RR 7.35-7.45) - H+ increasing from 40 to 100nmol/L! - Acidosis is largely buffered by converting: - HCO3¯ + H+→ H2CO3 → H2O + CO2 - HCO3 usually falls less than 10 mmol/L at presentation (RI 22-29 mmol/L) - Characteristic compensatory hyperventilation with slow deep breaths (Kussmaul's respirations) in an effort to remove CO2 ## Raised anion gap metabolic acidosis - If unsure of cause of metabolic acidosis, the anion gap is a simple diagnostic tool - Anion gap = Na+ - (CI¯ + HCO3¯) - In DKA, the anion gap may be 20-40 mmol/L (RI <15 mmol/L) - due to the unmeasured anions (β-hydroxybuyrate & acetacetate) - Other causes of raised anion gap metabolic acidosis include: - Lactic acidosis (secondary to severe dehydration & shock) - Starvation ketosis - Alcoholic ketoacidosis - Uremic acidosis in renal failure - Toxic ingestions (salicylate, methanol, ethylene glycol) ## Volume Status - Volume contraction is a hallmark of diabetic ketoacidosis - Driven by hyperosmolality secondary to hyperglycaemia - Mild diabetic ketoacidosis - Osmotic diuresis - Movement of H2O from the intracellular to extracellular space - Partially counterbalanced by polydipsia - Severe diabetic ketoacidosis - Inability to maintain fluid balance (babies, elderly, sick) - Fluid deficits of 5-10 L are common - Hypovolaemic shock - Lactic acidosis, uraemic acidosis - Hypotension - Rapid, weak, thready pulse - Thirst & dry mouth - Cold & mottled skin ## Potassium disturbance - Factors ↑ extracellular fluid (ECF) K+ - Shift of K+ to extracellular space due to acidosis (H + exchanged for K+ in ECF) - Insulin required to stimulate Na+/K+ ATPase - Factors ↓ ECF K + - Increased K+ excretion due to raised plasma K + - secondary hyperaldosteronism - occasionally vomiting - Commonly N/↑ plasma K+ masking a total body K+ deficiency - Both hyper- & hypokalaemia can result in cardiac arrhythmias ## Pathogenesis of DKA and HHS; Triggers include stress, infection, and insufficient insulin. FFA: free fatty acid; HHS: hyperosmolar hyperglycemic state From: Kitabchi AE, Umpierrez GE, Miles JM, et al. Diabetes Care. 2009, 32:1335-43; used with permission | | | | | | :-------------------- | :------------------------------- | :---------------------------------- | :-------------------- | | **Absolute Insulin Deficiency** | **Counterregulatory Hormones** | **Relative Insulin Deficiency** | | | ↑ Lipolysis | Protein synthesis | Absent or minimal ketogenesis | | | ++ | ↑Proteolysis | | | | ↑ FFA to liver | ↑Gluconeogenic substrates | | | | ↑ Ketogenesis | ↑Gluconeogenesis | ↑Glycogenolysis | | | Alkali reserve | | | | | ↑ Ketoacidosis | | | | | Triacylglycerol | | | | | Hyperlipidemia | | | Hyperosmolarity | | | Hyperglycaemia | | | | | Glycosuria (osmotic diuresis) | | | | | Loss of water and electrolytes | | | | | ↓ | | | | | Dehydration | | | | | Decreased fluid intake | | | | | Impaired renal function | | | | | | | **DKA** | | | | | **HHS** | Ref Diabetic ketoacidosis - Etiology | BMJ Best Practice US ## Chronic Complications - The long term management of diabetes is to minimise the risk of the patient developing chronic complications - All the main complications of diabetes seem to stem from effects on the vasculature - **Microvascular disease** - Retinopathy (leading cause of blindness) - Nephropathy (leading cause of end stage renal disease) - Neuropathy - **Atherosclerosis** - Coronary artery disease - Cerebrovascular accidents - Peripheral vascular disease - There are a variety of modifications that patient's need to make to minimise these risks - Good glucose control - Smoking cessation - Healthy lifestyle habits (nutrition, exercise) - Controlling hypertension - Managing dyslipidaemia ## DCCT: A1C and Microvascular Complications - A chart shows a graph of relative risk versus HbA1c (mmol/l) for Retinopathy, Nephropathy, Neuropathy, Microalbumin. The values on the x axis (HbA1c, mmol/l) go from 42 to 108, split into increments of 11. - The y axis (Relative Risk) goes from 1 to 15. For HbA1c values of 42-75, the Relative Risk value for the four conditions is mostly negligible. For HbA1c values of 75-108, the Relative Risk value increases with increasing HbA1c values. - **Skyler JS. Endocrinol Metab Clin North Am. 1996;25:243-254.** ## Kidney Disease ## Diabetic Kidney Disease - DM is the most common predisposing factor for developing chronic kidney disease and requiring dialysis - **Urinary Albumin Excretion Rate (AER, ACR a.k.a. microalbuminuria)** - This is a marker of dysfunction of the renal glomeruli as it indicates that albumin is leaking through the damaged glomeruli - It may present intermittently in T1DM 3-5 years after first diagnosis and over time in some patients becomes persistent. - Its presence and quantity are risk factors for chronic kidney disease - risk marker for other microvascular & atherosclerotic diseases - **Glomerular Filtration Rate** - While a reduction in glomerular filtration rate can have multiple causes, a reduction of GFR over time in diabetes usually indicates a loss of functioning nephrons - While there are methods available to directly measure GFR, in clinical practice this is usually estimated based on the serum creatinine of the patient - The calculation used in our laboratory takes into account the gender and age of the patient. No factors for the race are utilised (in keeping with current guidelines) - **Other** - Kidney Failure Risk Equation (KFRE) risk prediction tool for a kidney replacement therapy in the next two or five years in individuals with chronic kidney disease (CKD) stages 3a-5 ## CKD Classification CKD is classified based on: - Cause (C) - GFR (G) - Albuminuria (A) | GFR categories (ml/min/1.73m²) Description and range | GFR | Albuminuria categories Description and range | A1 | A2 | A3 | | :-------------------------------------------------- | :-- | :------------------------------------------- | :------------- | :------------- | :------------- | | G1 Normal or high | ≥90 | | 1 if CKD | Treat | Refer** | | G2 Mildly decreased | 60-89 | | 1 if CKD | Treat | Refer** | | G3a Mildly to moderately decreased | 45-59 | | Treat | Treat | Refer | | G3b Moderately to severely decreased | 30-44 | | Treat | Treat | Refer | | G4 Severely decreased | 15-29 | | Refer* | Refer* | Refer | | G5 Kidney failure | <15 | | Refer | Refer | Refer | ## Atherosclerotic Disease - Similar to atherosclerosis in non-diabetic subjects, but more rapidly progressive and extensive - Insulin resistance and hyperglycaemia both accelerate atherosclerosis by instigating endothelial cell dysfunction and dyslipidaemia ## Diabetic Dyslipidaemia - Insulin resistance results in: - Increasing free fatty acid (FFA) release from adipose tissue - FFA are are converted to triglycerides in liver and repackaged as Very Low Density Lipoprotein (VLDL) - Metabolism of the excess VLDL results in low levels of HDL and increased numbers of small dense LDL particles which predispose diabetics to atherosclerosis - This risk can be managed through good diabetic control and the use of lipid modifying drugs such as statins - Diabetic dyslipidaemia is usually monitored using routine lipid profile parameters - Total & LDL cholesterol often normal & falsely reassuring as routine tests don't clearly identify patients with an increased number of proatherogenic small dense LDL particles that contain little cholesterol - However this can usually be inferred as these patients generally have low HDL cholesterol levels and raised triglyceride levels ## Monitoring ### Lab Investigations - **HbA1c** - used to: - Monitor long-term glycaemic control - Evaluate and adjust therapy - Measure risk for the development of microvascular complications - Screen for and diagnose diabetes - Assess quality of diabetes care - Evaluate new medications for diabetes - Available formal lab and point of care testing (POCT not for diagnosis) - **Alternatives to HbA1c** - Role when the use of HbA1c is limited due to clinical reasons eg Hgb variants - These are not standardised, not widely available - No evidence based – clinical decision/limits of cut-points currently - Examples Fructosamine, glycated albumin ### Self monitoring: Glucose Monitoring - There are several self-monitoring devices shown. - **ONETOUCH VeriolQ** - **CONTOUR** - **ACCU-CHEK Aviva** - **FreeStyle Lite** - **ACCU-CHEK Mobile** ### Continuous Glucose Monitoring - An image shows: - A device which is attached to the skin - A smartphone with a graph showing a glucose reading of 110 mg/dL - An Apple Watch with graph showing a glucose reading of 110 mg/dL - **NUM System with Share and the ollow apps are available in the US only** ### Graphing Glycaemic Control - Two graphs show glucose (mmol/L) versus Time (00:00 - 22:00) - The graphs shows the curves of Glucose readings throughout the day. - The graph indicates the 10th to 90th percentile, and the 25th to 75th percentile. - The median value has been plotted on the graph and has been indicated. - The target range for glucose reading has also been indicated on the graph. ### Ketone Meters - There are three Ketone Meters shown in the image. - **CareTouch Gen** - **Nova Max** - **Precision Xtra** ## Case Scenarios