Diabetes cases are increasing with every passing day, so it becomes the responsibility of every healthcare professional to prevent and treat this epidemic. This article gives insight into the latest guidelines from the American Association of Clinical Endocrinology AACE for diagnosing and managing diabetes.

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Diagnosing diabetes and the current screening protocol for prediabetes and diabetes

Prediabetes is identified by the presence of:

• Impaired fasting glucose (IFG) (100 to 125 mg/dL),
• Impaired glucose tolerance (IGT) which is a plasma glucose value of 140-199 mg/dL 2 hours after ingesting 75 g of glucose, or
• HbA1C value between 5.7% and 6.4%.

Diabetes mellitus diagnosis is based on either one or more of the following criteria:

• A fasting plasma glucose (FPG) of >126mg/dl (after at least 8 hours of fasting) 
• The plasma glucose (PG) concentration of >200 mg/dL 2 h after ingesting a 75-g oral glucose load after an overnight fast of at least 8 hours
• Patients with symptoms of hyperglycemia characterised by polyuria, polydipsia, polyphagia and a random plasma glucose concentration of 200 mg/dL
• Patients having Hemoglobin A1C (HbA1C) level >6.5%

Diagnosis of diabetes requires two abnormal test results, either from the same sample or two abnormal results on samples drawn on different days. Type 2 Diabetes is characterised by progressive loss of beta cells insulin secretion along with variable changes in sensitivity towards insulin. As per recommendation, all adults of 35 years with risk factors should be screened for Diabetes.

Type 1 diabetes (T1D) -The patients have marked insulin deficiency which results in hyperglycemia along with positive autoantibody tests to:

• glutamic acid decarboxylase (GAD65)
• pancreatic islet b cells (tyrosine phosphatase IA-2)
• IA-2b zinc transporter (ZnT8)

Gestational diabetes mellitus (GDM) - It is defined as carbohydrate intolerance resulting in hyperglycemia that begins or is first recognised during pregnancy and which resolves postpartum. Pregnant women with risk factors for diabetes should be screened at the first prenatal visit for undiagnosed T2D using the standard criteria:

1. All pregnant women should be screened for GDM at 24 to 28 weeks gestation. Diagnose GDM with either the one-step or the two-step approach.
2. The one-step approach uses a 2-h 75-g oral glucose tolerance test (OGTT) after 8 hr of fasting with diagnostic cutoffs of one or more symptoms such as:

• Fasting Plasma glucose >92 mg/ dL
• 1-hr plasma glucose >180 mg/dL
• 2-hr plasma glucose >153 mg/dL

The two-step approach uses a non-fasting 1-hr 50-g glucose challenge test with a 1-hr plasma glucose screening threshold of 130 or 140 mg/dL.

Monogenic diabetes mellitus - Always consider evaluation for monogenic DM in any child or young adult with an atypical presentation, clinical course, or response to therapy. Monogenic DM includes neonatal diabetes & nonautoimmune diabetes of multiple genetic causes, also known as maturity-onset diabetes of the young (MODY). Most children with DM occurring under age 6 mo of age have a monogenic cause as autoimmune T1D rarely occurs before 6 months of age.

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Glycemic treatment goals for persons with diabetes mellitus

Outpatient glucose targets for non-pregnant adults

1. An HBA1C level of <6.5% is recommended, if it can be achieved safely.
2. To achieve this target HbA1C level, FPG may need to be <110mg/dL and the 2-h postprandial glucose (PG) may need to be <140 mg/dL.
3. As per recommendation glucose targets should be individualised with consideration for life expectancy, cardiovascular disease (CVD) risk factors, disease duration, presence or absence of micro- and macrovascular complications, co-morbid conditions, and risk for hypoglycemia, as well as a person’s cognitive and psychological status.
4. Less stringent glycemic goals (HBA1C 7% to 8%) should be targeted in persons with a history of severe hypoglycemia, hypoglycemia unawareness, limited life expectancy, Chronic Kidney Disease CKD, extensive co-morbid conditions, or long-standing diabetes mellitus in which the HBA1C goal has been difficult to attain despite intensive efforts, so long as the person remains free of hyperglycemia-associated symptoms.

Inpatient glucose targets for non-pregnant adults

As per recommendation for most hospitalised persons with hyperglycemia in both the intensive care unit (ICU) and non-ICU settings, a plasma glucose range of 140-180 mg/dL should be maintained, provided this target can be safely achieved without causing hypoglycemia.

Outpatient glucose targets for pregnant women

In women with GDM, the following glucose goals are recommended:

• Fasting glucose concentration <95 mg/dL and
• Either a 1-h postmeal glucose value <140 mg/dL, or
• 2-h post-meal glucose value <120 mg/dL

The recommendation for women with preexisting T1D or T2D who become pregnant is to maintain glucose in below mentioned range, provided this target is safely achieved without significant hypoglycemia. HbA1C of <6% along with:

• Premeal, bedtime, and overnight glucose values between < 95 mg/dL
• 1-h postprandial value between 110- 140 mg/dL
• 2-h glucose 100 -120 mg/dL

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Glucose monitoring frequency

HbA1C should be measured at least 6 months in all persons with DM and at least every three months in persons not maintaining their glycemic target. All patients who are on insulin therapy should use continuous glucose monitoring (CGM) or perform blood glucose monitoring (BGM) a minimum of twice daily and ideally before any insulin injection.

CGM is the preferred method of glucose monitoring for all individuals with T1D In Type 1 Diabetes patients real-time continuous glucose monitoring (rtCGM) or intermittently scanned continuous glucose monitoring (isCGM) is recommended, regardless of insulin delivery system. This type of monitoring helps to improve HbA1C levels and also reduces the risk of hypoglycemia and Diabetic ketoacidosis in such patients.

rtCGM or isCGM is also recommended for patients with type 2 diabetes who are treated with insulin therapy, or patients who are at high risk for hypoglycemia and/or with hypoglycemia unawareness.

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Management

1. Management of prediabetes

1. Prediabetes is a metabolic disease and the treating physicians should actively treat people diagnosed with prediabetes in order to prevent or at least delay progression to type 2 diabetes and its associated CVD complications.
2. As per recommendation patients should be counselled about lifestyle modification which includes a healthy meal plan, regular physical activity (at least 150 min/week of moderate exercise) and behavioural health practices along with weight loss in persons with obesity/adiposity-based chronic disease (ABCD).
3. The Mediterranean diet should be considered to reduce the progression to type 2 diabetes. Low-fat diet, vegetarian and DASH meals can also be considered in patients with prediabetes.
4. Treating physicians should manage and monitor CVD risk factors in prediabetes and metabolic syndrome, including elevated BP, dyslipidemia, and excessive weight, with the same targets as for a person with T2D.
5. As per recommendations prediabetic patients with obesity/ABCD should be advised for weight loss of at least 7% to 10% for prevention of T2DM. Obesity medications like phentermine/topiramate ER, liraglutide 3 mg, orlistat or weekly semaglutide 2.4 mg, in conjunction with lifestyle therapy should be considered.
6. To date, no medications have been approved for the treatment of prediabetes, diabetes medications like metformin, acarbose, pioglitazone, or GLP-1RA can be considered in persons with prediabetes or in persons who also have ABCD and remain glucose-intolerant following weight loss.

2. Management of type 2 diabetes

1. The aim of therapy in type 2 diabetes is to control hyperglycemia, to conserve beta cells of the pancreas, overcome insulin resistance and prevent CV morbidities.
2. All persons with diabetes should be prescribed, counselled and supported in lifestyle interventions that include a healthy meal plan, regular physical activity, and healthful behaviour practices.
3. Individualised medical nutrition therapy (MNT) should be provided at the time of diagnosis via evaluation and counselling by a trained registered dietitian, certified nutritionist, or a clinician knowledgeable in nutrition.
4. Health care professionals should emphasise foods and nutrients that contribute to high “diet quality” scores as assessed by the Healthy Eating Index (HEI); high HEI is associated with reduced risks of DM, CVD, and mortality and includes fruits, nonstarchy vegetables, whole grains, nuts, legumes, and fish, with limited consumption of added sugars, refined grains, red meat, and processed meats.
5. Lifestyle intervention in persons with DM should include an individualised prescription for physical activity involving aerobic and resistance exercise and reduction in sedentary behaviour with a prescription for aerobic physical activity of at least 150 min/week of moderate exercise performed during 3 to 5 sessions per week.

Anti-hyperglycemic pharmacotherapy for people with type 2 diabetes

In patients with diabetes Glycemic targets include HbA1C, BGM, and, for those using CGM, achievement of CGM targets such as time in range (TIR), percentage in low and very low range, time above range, and glycemic variability nonglycemic targets include avoidance of hypoglycemia, control of BP, lipids, other CVD risk factors, and achieving and maintaining a healthy body weight.

1. Treating physicians should prescribe a GLP-1 RA or an SGLT2i with proven efficacy for the specific condition(s) of the person with T2D if there is established or high risk for ASCVD, Heart failure, and/or CKD,
2. Metformin is often the preferred initial therapy. Other agents may be appropriate as first-line or in addition to metformin to reduce BG and/or to address specific comorbidities(such as ASCVD, HF, CKD, obesity, NAFLD), independent of glucose-lowering effects.
3. Early combination pharmacotherapy should be considered for some recently diagnosed individuals with T2D and more severe hyperglycemia (HBA1C >7.5%), unlikely to attain the HBA1C target with a single agent, which usually includes metformin plus another agent that does not cause hypoglycemia, especially a GLP-1RA, SGLT2i, or dipeptidyl peptidase 4 (DPP-4) inhibitor.
4. Dual- or possibly triple-combination pharmacotherapy usually including metformin along with lifestyle modification can be started for newly diagnosed persons with T2D and an entry HBA1C >9.0% and/or >1.5% above target.
5. Basal insulin along with noninsulin therapy is recommended if there are significant signs or symptoms of hyperglycemia, especially including catabolism (eg, weight loss) or a very high HBA1C >10% (86 mmol/mol) or BG levels (>300 mg/dL [16.7 mmol/L]).
6. Persons with T2D who start on metformin should continue it unless intolerance or contraindications occur. When intensification of antihyperglycemic treatment is required, other agents should be added to metformin.
7. Insulin should be prescribed for persons with T2D when noninsulin antihyperglycemic therapy fails to achieve target glycemic control or when a person has symptomatic hyperglycemia.
8. Long-acting basal insulin analogues are the recommended initial choice of insulin therapy for persons with T2D. The insulin analogues glargine (U100 or U300), degludec (U100 or U200), or detemir are preferred over intermediate-acting Neutral Protamine Hagedorn (NPH) insulin because analogue insulins have demonstrated less hypoglycemia in some studies.
9. Before adding meal-time insulin for postprandial glycemic control in patients with T2D receiving basal insulin and not at goal HbA1C can have significantly improved glycemia by the addition of a GLP-1 RA or being switched to a fixed-ratio combination basal insulin GLP-1 RA (GlarLixi or IdegLira).
10. When control of postprandial hyperglycemia is needed and basal insulin and a GLP-1 RA are already being used, preference should be given to rapid-acting insulins (the analogues lispro, aspart, and glulisine or the rapid-acting inhaled human insulin powder) over regular human insulin. As the former is associated with less risk of hypoglycemia.
11. Ultra-rapid-acting insulins (faster-acting insulin aspart, lispro aabc, and [human insulin] inhalation powder) may allow a decrease in the time between insulin administration and food intake and reduce the postprandial peak of plasma glucose as compared with rapid-acting insulins.
12. Basal-bolus insulin regimens or continuous subcutaneous insulin infusion (CSII) (ie, insulin pump) allow for adjustment of insulin doses according to carbohydrate intake and activity levels and are recommended for intensive insulin therapy in persons with T2D.
13. Premixed insulin formulations (fixed combinations of shorter- and longer-acting components) of human or analogue insulin may be considered for persons with T2D who have consistent dietary and exercise patterns and in whom adherence to more intensive insulin regimens is problematic.
14. In persons with T2D who are treated with basal-bolus insulin therapy, adding a GLP-1 RA, switching to a fixed-ratio combination of a GLP-1 RA and basal insulin, or adding an SGLT2i or pramlintide (less commonly used) may be able to reduce postprandial hyperglycemia, HbA1C, and weight. GLP-1 RAs may also allow the reduction or discontinuation of bolus insulin in some individuals.

3. Management of type 1 Diabetes

1. All persons with T1D should be treated with insulin.
2. Physiologic insulin replacement regimens, which provide both basal and prandial (meal-related or bolus) insulin, are recommended for most persons with T1D.
3. Achievement of glucose targets using either MDI of insulin or CSII, is needed to prevent the development of life-threatening crises, such as acute hyperglycemic crisis (DKA and hyperglycemic hyperosmolar state) and catabolic state.
4. A multi-component self-management DM education program is recommended for persons with T1D.individuals should be counselled and educated on the topics of a healthy lifestyle, and insulin technique including prandial insulin dosing guided by carbohydrate counting and diet adjustments for special situations, such as physical activity and prolonged fasting. Instruction is also needed on how to deal with sick days and prevention of DKA and hypoglycemia, and other relevant issues.
5. The ideal insulin regimen should be personalised to an individual’s needs and glycemic targets, attempting to better emulate physiological insulin replacement to maintain near normoglycemia, to prevent the development and progression of DM complications, while minimising hypoglycemia and providing flexibility for specific daily life situations/scenarios such as exercise, sleep, acute illness, psychological stress, etc.
6. Insulin regimens usually should involve the use of insulin analogues for most persons with T1D and include the following approaches:
   1. MDI, which usually involves 1 to 2 subcutaneous injections daily of basal insulin to suppress gluconeogenesis and to control glycemia between meals and overnight, and subcutaneous injections of prandial insulin or use of inhaled insulin before each meal to control meal-related glycemic excursions.
   2. Insulin pump therapy (CSII) provides constant/continuous infusion of fast-acting insulin driven by mechanical force and delivered via a cannula inserted under the skin. CSII can improve (or enhance) glycemic control and should be an option for insulin delivery for appropriate persons with DM.
   3. Automated insulin delivery systems (AIDs), which include an insulin pump, an integrated CGM, and a computer software algorithm, aim to better emulate physiological insulin replacement and achieve glycemic targets.
   4. Open-loop (use of a pump and sensor which do not communicate) and sensor-augmented pump (SAP) systems: (CGM communicates with pump facilitating needed adjustments to basal rate; temporary interruption of insulin delivery when glucose levels are low or forecast to be low within 30 min). An insulin pump with a CGM or an SAP is recommended to manage persons with DM treated with intensive insulin management who prefer not to use AIDs or have no access to them.

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Management of hypoglycemia

1. Oral intake of rapidly absorbed glucose (eg, glucose tablets or dietary sugar like fruit juice) followed by a snack or meal containing both protein and carbohydrates (eg, cheese and crackers or a peanut butter sandwich) should be used to treat hypoglycemia (measured glucose <70 mg/dL [3.9 mmol/L]) if a person is able to safely swallow.
2. Glucagon should be used to correct hypoglycemia if individuals are unable or unwilling to ingest carbohydrates orally. If there is no response after 15 min, an additional same dose may be administered. As soon as the individual is awake and able to swallow, they should receive a rapidly absorbed source of carbohydrates.
3. Persons with severe hypoglycemia with altered mental status or with prolonged hypoglycemia need to be hospitalised and administered I/V dextrose or glucagon injection.
4. If an individual has hypoglycemic unawareness and hypoglycemia-associated autonomic failure, several weeks of hypoglycemia avoidance may at least partially reverse hypoglycemia unawareness and may reduce the risk or prevent the recurrence of severe hypoglycemia. Adjustment of an individual's long-term antihyperglycemic regimen may be necessary to further avoid the recurrence of hypoglycemia.
5. In persons with T2D who develop hypoglycemia and are being treated with alpha-glucosidase inhibitors or with pancreatic diabetes, oral glucose or lactose-containing foods (dairy products) must be given because alpha-glucosidase inhibitors inhibit the breakdown and absorption of complex carbohydrates and disaccharides (eg, table sugars or starches).
6. Persons at risk for hypoglycemia should perform frequent BGM or preferably use CGM devices.

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Management of diabetes mellitus in the hospital

1. All hospitalised persons should have laboratory glucose testing on admission. Persons with DM or with admission hyperglycemia >140 mg/dL should have glucose monitoring during hospitalisation.
2. Hospitalised persons with hyperglycemia but without known DM should have HbA1C measured to identify pre-existing DM and inform discharge planning.
3. Initiate bedside point-of-care (POC) capillary glucose monitoring at an appropriately chosen schedule to guide therapy for hyperglycemia during hospitalisation in all persons with DM, persons without prior DM who have hyperglycemia, and persons receiving therapies with a high risk of hyperglycemia, such as corticosteroids and enteral or parenteral nutrition.
4. For hospitalised persons with DM eating on a regular schedule, check POC BG before each meal and at bedtime, if clinically indicated. In hospitalised persons who are not eating (e.g., NPO [anything by mouth] or continuous feeding), initially check POC BG at least every 4 to 6 hours. Additional checks may be warranted for those at higher risk of hypoglycemia. For those on intravenous (IV) insulin, POC BG should be obtained from every 30 min to every 2 hours.
5. For critically ill persons, IV insulin infusion is recommended to treat persistent hyperglycemia in the ICU using validated protocols that allow adjustment of insulin dose for glycemic excursions based on prespecified glucose targets. For those receiving IV insulin, POC testing should be performed every 30 to 120 min.
6. The insulin regimen for hospitalised persons with satisfactory meal intake should include basal, prandial, and correction doses. For those without adequate food intake, a regimen of basal, prandial, and correction doses should be used as necessary for glycemic control. Exclusive use of “sliding-scale” insulin should only be used for those whose glucose is in the target range most of the time, and only occasionally exceed it.
7. The management of hyperglycemic emergencies, including DKA and hyperosmolar state, should include fully adequate fluid resuscitation to correct fluid deficits, electrolyte replacement (potassium), and insulin therapy. Simultaneously continued infusion of insulin and dextrose solutions after correction of hyperglycemia is often required until DKA resolves to avoid hypoglycemia.
8. Transition from IV insulin in the ICU to a subcutaneous insulin regimen is typically required when acidosis is resolved, and a person is no longer critically ill.
9. For hospitalised persons with T2D and mild admission hyperglycemia (glucose <180 mg/dL), a personalised approach is recommended for the use of noninsulin agents alone or in combination with basal insulin, aiming for the most efficacious regimen with the lowest hypoglycemic risk. For some hospitalised persons with T2D, DPP-4 inhibitors plus correction doses with rapid-acting insulin, or basal insulin plus DPP-4 inhibitors may be sufficient.

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Management of diabetes mellitus in pregnancy

1. For women diagnosed with GDM, the following treatment goals are recommended: preprandial glucose concentration <95 mg/dL and either 1 hour postmeal glucose<140 mg/dL or 2 hours postmeal glucose <120 mg/dL to decrease adverse fetal outcomes.
2. All women with preexisting DM (T1D, T2D, or previous GDM) need access to preconception care and counselling to ensure adequate nutrition, healthy weight, and glucose control before conception, during pregnancy, and in the postpartum period.
3. Insulin is the preferred therapeutic choice for pregnant women with GDM or T2D, but metformin (category B for pregnancy) with accumulating clinical evidence of metformin’s safety during the first trimester and beyond. Metformin has been shown to improve pregnancy and fetal outcomes except for increased rates of infants with small gestational age and later onset of obesity.
4. Rapid-acting insulin analogues (insulin-lispro, insulin-aspart) should be used to treat postprandial hyperglycemia in pregnant women.
5. Options for basal insulin include long-acting insulin (eg, NPH, detemir) or rapid-acting insulin via a CSII. Regular insulin, although not recommended as first-line therapy, is acceptable to use in managing pregnant women with DM when rapid-acting insulin analogues are not available.

Stay tuned for Part 2 of this article!

Disclaimer- The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of M3 India.

About the author of this article: Dr Hitesh Saraogi is a diabetologist, physician and an obesity specialist at Dhanvantari Hospital, Raj Nagar Extension, Ghaziabad.