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Guidelines on Diabetes: Diagnosis & Management

NEW - Standard of Medical Care in Diabetes 2009 - [pdf]

  1. Diagnosis
  2. Medications for Type 2 Diabetes
  3. Glycemic Goals of Therapy
  4. Recommended Screening Intervals
  5. Preventing Cardiovascular Disease
  6. Prevention of Diabetic Nephropathy
  7. References

Insulin resistance is common among HIV-infected; diabetes less so but still has a 2- to 4-fold higher incidence than the general population. Risk factors for diabetes among our patient population includes: fat accumulation (especially truncal) or peripheral wasting from lipodystrophy, family history of diabetes, obesity, age, hepatitis C, low CD4 nadir, black/Hispanic race. Presence of certain medications may also contribute to this risk: protease inhibitors (indinavir >> nelfinavir, ritonavir, Kaletra > saquinavir, (fos)amprenavir > atazanavir), steroids, Megace, immunosuppressants, atypical antipsychotics such as olanzapine.”

Madison Metabolic Clinic: Consider referral to the Madison Metabolic Clinic for those patients with hypertension, dyslipidemias, lipodystrophy and diabetes who need extra managment of these disease states.

I. Diagnosis

Diagnosis of diabetes in an individual can be made in one of four ways:

  • A1c value ≥6.5%. The test should be performed in a laboratory using a method that is National Glycohemoglobin Standardization Program–certified and standardized to the Diabetes. *Control and Complications Trial assay.*
  • Fasting plasma glucose level ≥126 mg/dL (7.0 mmol/L). Fasting is defined as
  • Two-hour plasma glucose level ≥200 mg/dL (11.1 mmol/L) during an oral glucose tolerance test. The test should be performed as described by the World Health Organization, using a glucose load containing the equivalent of 75 g of anhydrous glucose dissolved in water.*  This is the standard for diagnosis of gestational diabetes in pregnant patients.
  • In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose level ≥200 mg/dL (11.1 mmol/L).

    *In the absence of unequivocal hyperglycemia, criteria 1 through 3 should be confirmed by repeat testing.

    II. Medications for Type 2 Diabetes Mellitus

    • One of the most common errors in diabetes management is a slow stepwise treatment approach when a more aggressive initial response is appropriate.
    • In order to rationally treat a patient with diabetes it is important to recognize the expected decline in HgA1c for each class of medication. For example the initial regimen for a diabetic with a HgA1c=11 mg/dL should include insulin since oral therapy would be unlikely to lower HgA1c to <7.
    • Patients can have transient improvement in beta cell function after initial control of hyperglycemia, but typically type 2 diabetes is a progressive disease and patients likely will require more intensive therapy over time.
    • Diet and Exercise which on average lowers HgA1c 0.5-2.0 mg/dL.

    Sulfonylureas (glipizide, glyburide, etc.) and the newer glitinides (nateglinide and repaglinidine)

      • Both act by inducing insulin secretion
      • The glitinides have a more rapid action of onset and shorter duration of effect than sulfonylureas and are used with meals
      • The average decrease in HgA1c is 1-2 mg/dL
      • Both these medications can lead to hypoglycemia and weight gain

    Metformin

      • Leads to an average decrease in HgA1c of 1-2 mg/dL by reducing hepatic gluconeogenesis
      • Lactic acidosis is rare (<3 case per 100,000 patients treated)
      • Contraindicated in patients with CHF, renal or hepatic dysfunction, or binge alcoholism
      • Metformin should be held shortly before surgical procedures and before radiologic studies involving intravenous contrast
      • Metformin does not cause weight gain and should be given first line in obese type 2 diabetics

    α-Glycosidse inhibitors (acarbose and miglitol)

      • Act by inhibiting absorption of carbohydrates
      • On average lower HgA1c by 0.5-1.0 mg/dL
      • Use is limited by disagreeable gastrointestinal symptoms
      • Acarbose is contraindicated in cirrhosis and requires LFT monitoring.

    Thiazolidinediones (rosiglitazone and pioglitazone)

      • Act by increasing peripheral sensitivity to insulin
      • On average decrease HgA1c 0.5-1.0 mg/dL
      • Their use is contraindicated in heart failure and complicated by edema and weight gain

    Incretin mimetic (exenetide)

      • Enhances glucose-dependent insulin secretion
      • FDA-approved for use as an adjunct for those failing oral agents
      • At 10mcg sc bid, averaged HgA1c of about 1mg/dL
      • Adverse effects include nausea and hypoglycemia
      • Similar efficacy to bedtime insulin (without the weight gain) when added to failing oral regimen, but substantially more expensive

    Amylin analogue (pramlintide)

      • Suppresses postprandial glucagons secretion and slows gastric emptying
      • HgA1c decreased on average 0.1-0.6 mg/dL with 1-3 pounds of weight loss
      • Associated with severe hypoglycemia when used in conjunction with insulin secondary to slowed absorption of carbohydrates
      • Manufacturer recommends reducing insulin dose 50% when initiating pramlintide to reduce risk of hypoglycemia

    Insulin has many formulations

      • Indications for starting insulin are:
        • 1) new diagnosis of severe, symptomatic hyperglycemia
        • 2) co-morbid conditions such as CHF, renal or hepatic disease, active infection that may make control difficult with oral medications
        • 3) pregnancy
        • 4) intolerance to oral medications.
      • Differ in their time to peak activity and duration of action
      • Early in the disease course of type 2 diabetes, patient may need only long-acting insulin
      • As diabetes progresses, will likely need mealtime and long-acting insulin to adequately control sugars
      • When fasting AM sugars are adequate but sugars during the day are poorly controlled, the patient needs mealtime insulin and more intensive blood glucose monitoring to meet glycemic goals
      • Typical starting insulin dose is 10-20 units/day
      • Insulin use results in weight gain and can lead to hypoglycemia

      From: “In the Clinic – Type 2 Diabetes.” Annals of Internal Medicine, 2007 Jan 2;146(1): ITC1-15.

    III. Glycemic Goals of Therapy

    The goal of therapy is HgA1c ≤7 mg/dL.

    Secondary goals are a fasting glucose between 90-130 mg/dL and a peak post-prandial glucose≤180.

    IV. Recommended Screening Intervals

    Hemoglobin A1c

    • Reflects glycemic control over the past 2-3 months
    • Should be checked at least twice a year in patients on stable therapy and meeting glycemic goals
    • In patients not meeting glycemic goals or with a change in therapy, HgA1c should be checked quarterly

    Cholesterol (lipid panel)

    • Should be checked at least annually and more frequently if needed to meet goals
    • Most accurate if performed after a 9-12 hour fast
    • On average, a non-fasting value artificially raises TG levels 20-30 mg/dL and falsely depresses LDL level 4-6 mg/dL

    Diabetic nephropathy

    • Annual screening should be performed with a spot urine sent for an albumin-to-creatinine ratio
    • Microalbuminuria is diagnosed by a ratio greater than 30 in two out of three tests in a six month period
    • Test subject to false positives (due to dehydration and other factors)
    • Patients with type 1 diabetes should be screened annually beginning 5 years after diabetes diagnosis while screening should be initiated in type 2 diabetics beginning at the time of diagnosis

    Diabetic retinopathy

    • Annual recommended.
    • However, on the advice of an eye professional less frequent exams (every 2-3 years) are acceptable in low risk patients
    • Patients with type 1 DM can wait 3-5 years after diabetes diagnosis before initiating annual screening while screening in patients with type 2 DM should begin at time of diagnosis

    Diabetic Foot

    • Annual exam to assess protective sensation, foot structure and biomechanics, vascular status, and skin integrity
    • Patient with neuropathy should have a visual inspection of their feet with every clinic visit

    V. Preventing Cardiovascular Disease

    Blood pressure

    • Goal in diabetics is 130/80
    • Initial choice of medication should probably be an ACE inhibitor (or an angiotensin receptor blocker if cough develops with an ACE inhibitor) due to its reno-protective effect
    • However, results from ALL-HAT (a large anti-hypertensive trial) suggest that a long-acting diuretic is equally efficacious
    • Third line therapy for hypertension in diabetics should be either a beta-blocker or a calcium channel blocker

    Aspirin

    • According to the American Diabetic Association, low dose aspirin (75mg-162 mg qd) should be used as primary prevention in patients with diabetes (Type 1 or 2) who are at increased cardiovascular risk, including those over 40 years of age or who have additional risk factors (family history of CAD, hypertension, smoking, dyslipidemia, or albuminuria)
    • Aspirin should be used as secondary prevention in patients with a history of vascular disease

    Lipids

    • Generally, goal is LDL<100
    • However, for patients with very high risk such as those with known coronary artery disease and diabetes an optional goal is an LDL <70.
    • Given that there is continued reduction of cardiac risks in decreasing cholesterol even to very low levels, if initiating a patient on drug therapy, one should attempt to reduce LDL at least 30% from baseline
    • If triglycerides are elevated one should calculate the non-HDL cholesterol (total cholesterol-HDL cholesterol)
    • Non-HDL cholesterol is a secondary goal of therapy and is set at 30 mg/dL above the LDL goal
    • In general, the initial drug of choice is a statin
    • For more details on cholesterol management refer to the cholesterol guidelines on this webpage

    VI. Prevention of Diabetic Nephropathy

    Blood pressure and glucose control are crucial in preventing renal damage.

    If albuminuria (micro or macro) develops an ACE inhibitor or an angiotensin receptor blocker should be initiated.

    Conflicting evidence regarding the use of a low-protein diet to prevent progression of kidney disease.

    VII. References

    The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group, Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs. diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), JAMA 2002;288:2981-97.

    American Diabetes Web Page (www.diabetes.org)

    Kaplan NM, Management of Hypertension in Patients with Type 2 Diabetes Mellitus, Ann Intern Med 2001;135:1079-1083.

    Nathan DM, Initial Management of Glycemia in Type 2 Diabetes Mellitus, NEJM 2002; 347:1342-9.

     

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