Management of diabetes mellitus in primary care

SCREENING AND PREVENTION ㅡ Screen asymptomatic patients at increased risk for diabetes mellitus (family history of diabetes in twin, sibling, or parent, obesity, gestational diabetes and history of impaired glucose tolerance). Use fasting glucose determination; fasting test is preferred since it is most sensitive of methods appropriate for asymptomatic adult populations when threshold for positive test is glucose > 126 mg/dL. For patients with fasting glucose > 126 mg/dL, proceed to confirmatory testing for presence of any of 3 diagnostic glucose abnormalities found on 2 separate days:

• Fasting plasma glucose > 126 mg/dL.
• Random plasma glucose > 200 mg/dL in person with diabetic symptoms.
• 2-hr postprandial plasma glucose level > 200 mg/dL after administration of equivalent of 75-g glucose load.

MANAGEMENT

All patients

Treat hyperglycemia aggressively. Attempt to normalize blood glucose; goal is HbA1C concentration < 7% and fasting glucose level < 126 mg/dL. Emphasize importance of maintaining ideal body weight. For obese patients, institute caloric restriction without compromising regularity of meal timing. Prescribe regular aerobic exercise. Prescribe balanced diet that achieves reduction in calories and saturated fat. Diagnose and aggressively treat all major additional atherosclerotic risk factors. Teach diabetic patients, (especially those on insulin Rx) how to monitor glycemic control daily with home blood glucose determinations. Assess long-term glucose control with HbA1C measurements 3–4 times/year. Carefully investigate causes of worsening hyperglycemia, like inadequate dose, increased caloric intake, failure to take insulin properly, occult infection (especially urinary tract), coronary ischemia, severe emotional stress, corticosteroid use, somogyi phenomenon, insulin resistance and growth hormone surge in early morning.

Regularly perform comprehensive history, physical examination, and selected laboratory studies (BUN, creatinine, urinalysis, lipid profile) for complications (e.g., coronary artery disease, nephropathy, cerebrovascular disease, peripheral vascular disease, neuropathy, and retinopathy). Closely monitor urinalysis and renal function for earliest signs of diabetic renal injury (e.g., microalbuminuria, microscopic hematuria, rising BUN and serum creatinine). At first sign of renal impairment, tighten glycemic control and prescribe angiotensin blockage, either with ACE inhibitor or angiotensin-receptor blocker. Also institute angiotensin blockage for patients with concurrent hypertension. Consider prophylactic angiotensin blockade for all diabetics, especially those who are middle-aged. When serum creatinine level reaches 3 mg/dL, obtain nephrology consultation regarding candidacy for dialysis or transplantation. Exercise caution in use of iodinated contrast agents, especially in setting of renal impairment. Refer all patients for annual diabetic eye exam to check for proliferative retinopathic changes. Emphasize foot care to diabetic patients with neuropathy or vascular insufficiency. Arrange regular podiatric care for such patients. Perform careful perioperative assessment of diabetic patients undergoing surgery. Pay particular attention to worsening hyperglycemia and diligently observe for infection and occult coronary artery diseases, particularly in those with evidence of microvascular disease.

Type 1 DM patients

Consider early institution of intensive insulin therapy to achieve very. Tight control (HbA1C 6–7%), especially for highly motivated patients willing to perform multiple daily glucose determinations and self-administer insulin according to results of tests. Consider less intensive insulin therapy or infusion pump technology for those unable to carry out intensive insulin regimen. For those attempting intensive insulin therapy, start with modest dose of long-acting insulin, such as Lantus (glargine-100 U)or Toujeo (glargine-300 U) or new long-acting preparations as Tresiba (insulin degludec), administered once/day in evening; start with dose of 15 U and increase in 2-U increments based on fasting glucose determinations; Begin program of short-acting insulin, such as regular insulin (Actrapid), started at 5 U administered 30–45 mins before meals and adjusted according to results of postprandial home glucose measurements; Prescribe human recombinant insulin for newly treated diabetics to minimize risks for insulin allergy, insulin resistance, and antibody development; Consider prescribing insulin lispro, aspart (or another fast-onset, very short-acting insulin), administered 10–15 mins before meals, to patients achieving tight control but bothered by frequent hypoglycemic episodes or inconvenience of standard regimen of regular insulin.

For those unable to carry out intensive insulin program, begin BID insulin regimen with intermediate-acting insulin (e.g. NPH), administered before breakfast and before evening meal for basal coverage, mixed with short-acting insulin (Actrapid) for prandial control; Adjust doses according to fasting and 4 PM. glucose determinations; Teach importance of regular caloric intake and regular spacing of meals to match peak insulin effects and activity schedules.

Type 2 DM patients

Emphasize weight reduction to ideal body weight as cornerstone of treatment for type 2 diabetes mellitus. Composition of diet is less important, but diet should have high ratio of polyunsaturated to saturated fat and contain cholesterol and complex carbohydrates. Diets low in protein may be beneficial in averting diabetic nephropathy. Prescribe practical program of regular exercise that fits patient's lifestyle; suggest ≥ 30 mins of exercise every other day. Continue exercise for its own sake, independent of any effect it may have on weight. If after 4–8 weeks of diet and exercise mild to moderate glucose intolerance persists (fasting glucose < 240 mg/dL), then in addition to diet and exercise; Begin oral therapy with biguanide (e.g. 500 mg metformin BID, with breakfast and evening meal) or second-generation sulfonylurea (e.g. 2.5 mg glyburide; 5 mg glipizide; or 1 mg glimepiride). Choose metformin if patient is obese. Increase oral agent dose every 1–2 weeks as needed. Consider twice daily dosing for glyburide and glipizide to maximize control or once-daily dosing of sustained-release glipizide. Advance until patient achieves glycemic goals or reaches maximum dose (20 mg/day for glyburide and glipizide; 8 mg/day for glimepiride). If after 4–8 weeks of monotherapy patient has not achieved glycemic goals, add second oral agent from different class to metformin (e.g. gliptins, SGLT-2 inhibitors or sulfonylurea) or add small dose of intermediate-acting insulin taken qhs (e.g. 10 U NPH). If sulfonylurea was starting drug, reduce sulfonylurea dose to avoid risk for prolonged hypoglycemia. If after 4–8 weeks of 2-drug oral agent therapy patient has not achieved control, consider adding dose of intermediate insulin qhs (e.g. 10 U of NPH) or third oral agent (e.g., a thiazolidinedione or acarbose). If adding thiazolidinediones (e.g., pioglitazone, rosiglitazone), start with low dose (for pioglitazone, 15 mg/day; for rosiglitazone, 2 mg/day), and monitor liver function (ALT) monthly for at least first several months, halting therapy at first sign of persistent elevation. Until thiazolidinediones are proved hepatically safe, consider them only if all other attempts to date have not achieved reasonable glycemic control and patient is reliable, free of underlying liver disease, and willing to have close monitoring of liver function tests. If program of insulin supplementation considered, be aware that initially supplementing oral agent therapy with small dose of insulin every night at bedtime may suffice but usually latter stages of type 2 diabetes mellitus require insulin as mainstay of therapy, supplemented by thiazolidinedione (e.g. pioglitazone, rosiglitazone) or metformin to reduce insulin resistance and keep dose manageable.

     If after 4–8 weeks of diet and exercise patient has not achieved treatment goals and is very symptomatic or manifests moderate to severe glucose intolerance (fasting glucose > 240 mg/dL), then begin insulin with intermediate-acting insulin preparation (NPH) at modest once-daily dose (e.g. 10 U before breakfast); Specify human recombinant insulin for newly treated diabetic patients to minimize risks for insulin allergy, insulin resistance, and antibody development. Advance insulin program according to glucose monitoring results with reference to target levels. If high doses of insulin, poor control, and weight gain become problems, consider adding metformin to insulin program to improve tissue responsiveness and reduce insulin requirements and weight gain. Thiazolidinediones can also improve insulin responsiveness and control, but do not halt weight gain.

REFERENCES

• Nathan, D.M., Buse, J.B., Davidson, M.B., Ferrannini, E., Holman, R.R., Sherwin, R. and Zinman, B. (2008). Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy: A consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care, [online] 32(1), pp.193–203. Available at: http://care.diabetesjournals.org/content/32/1/193?utm_source=twitterfeed&utm_medium=twitter