NOTE--The discussion below is focused primarily on Type 2 Diabetes Mellitus, though there is info applicable to type 1 also.
I. Initial workup
- History
- Confirm dx--see also "Definitions" section regarding diagnostic criteria
- Review previous & current tx
- Assess past & recent glycemic control--glucose, HbA1c
- Determine presence/stage of chronic complications--renal, ophthalmologic, neurologic (gastroparesis, erectile dysfunction in male, bladder), cardiovascular including PVD & CVA
- Review Sx
- Assess other cardiac risk factors
- Exercise habits
- Review h/o acute complications, including hypoglycemia, DKA, hyperosmolar hyperglycemic nonketotic sd, infection (skin, foot, GU, etc.)
- Check if on any meds that may affect blood sugar
- OB hx/contraception in female
- Physical exam
- Ht, Wt, BMI, BP
- Skin (including insulin injection sites)
- Eyes including fundi
- Oral cavity & dentition
- Thyroid
- Heart
- Abdomen
- Pulses
- Hands & feet
- Neurologic exam
- Assess glycemic control
- Fasting plasma glucose
- HbA1c--note this may be altered in pts with hemoglobinopathies
- Serum Creatinine
- Urinalysis with micro; culture if abnormal or symptomatic
- ECG
- Initiate routine diabetic screening as below (section IX.) with fasting lipids, microalbuminuria screen, retinopathy screen, etc.
- Workup for secondary causes, as clinically indicated:
- Hemochromatosis
- Hypothyroidism
- Pancreatic parenchymal disease
- Acromegaly
- Pheochromocytoma
- Cushing's disease
II. Lifestyle changes
- Exercise-consider ETT before starting, esp. if other risk factors for CAD
- Nutrition (dietitian referral)
- 50-60% of calories from CHO, mostly complex rather than simple
- 12-20% of calories as protein (less with renal disease)
- Restrict saturated fats to 10% of calories
- A stufy of a 13 pts with Type 2 DM randomized crossover-fashion to "standard" ADA diet vs. high-fiber diet (24g/d fiber vs. 50g/d) found sig. lower mean plasma glucose concentrations (13mg/dL lower) in the high-fiber group (NEJM 342:1392, 2000--AFP)
- Weight loss if obese
III. Control Hypertension, if present (click on link for discussion of pharmacologic management of hypertension in diabetics)
- Target BP
- JNC VII (JAMA 289:2560, 2003) & ADA say to 130/80, ACP-ASIM recommend 130-135/<80 (Ann. Int. Med. 138:587, 2003)
- In a randomized trial of target DBP of 80, 85, or 90; no sig. diffs. in clincial outcomes were seen among the groups overall, BUT among diabetics, 80mm Hg group had sig. lower risk for CV death than 85 or 90 groups and sig. lower risk for major CV events than 90 group ("HOT" study--Lancet 351:1755, 1998)
- In a randomized trial in 1,148 pts with type 2 DM and HTN to BP targets of 150/85 vs. 180/105. Over mean 8.4y f/u, tighter group had sig. lower risk CVA, diabetes-related mortality (RR 0.68), and various other DM-related endpoints; nonsig. reduction in all-cause mortality (UK Prospective Diabetes Study "UKPDS 38"--BMJ 317:703, 1998)
- 3,462 pts with type 2 DM randomized to "standard" vs. "tight" BP control; pts with lower BP's found to have lower risk of DM-related complications and DM-related death; there was no BP threshold below which further BP reduction appeared not to offer additional benefit (UK Prospective Diabetes Study "UKPDS 36"; BMJ 321:412, 2000--JW)
- In a randomized of 470 pts w/DM & HTN to DBP targets of 75mm Hg or 80-89mm Hg, at 5y f/u, no sig. diffs. in incidence of progression of nephropathy, retinopathy, or neuropathy, BUT all-cause mortality was sig. lower in tighter-control group (5.5% vs. 10.7%) (Appropriate Blood Pressure Control in Diabetes ("ABCD") study (Diab. Care 23(suppl. 2):54, 2000)
IV. Control Dyslipidemias if present
IV. If early-stage Diabetic Nephropathy is present:
- ACE Inhibitors will slow progression though ADA stops short of mandating their use in normotensive Type 2 diabetics with microalbuminuria ("clearly indicated [if] progression of albuminuria" is detected (1998 Practice Recommendations)
- Low-protein diet may slow progression
V. Smoking cessation if a smoker
VI. Contraception if female at risk for pregnancy
VII. GLYCEMIC CONTROL--Particularly important in women of childbearing age at risk for (or planning) pregnancy
- Goals
- ADA recommends "lowering blood glucose to or near normal levels in all patients"--these goals are the same for Type 1 & Type 2, though they admit "There is less certainty that the risk-benefit ratio of intensive insulin tx is as favorable in Type 2 pts as in Type 1 pts" (1998 Guidelines)
- Specific goals per ADA (figures are for whole blood glucose):
- Preprandial glucose 80-120 (change tx if > 140 or < 80)
- HS glucose 100-140 (change tx if > 160 or < 100)
- HbA1c < 7 (change tx if > 8)
- Value of tight vs. loose glycemic control
- Decreases risk of hyperosmolar coma
- Decreases sx (blurred vision, polyuria, polydipsia, etc.)
- Improves lipid profiles
- UK Prospective Diabetes Study--Demonstrated reduced risk of microvascular complications
- "UKPDS 33"--Lancet 352:837, 1998--JW
3,867 pts (median age 54y) with newly diagnosed type II DM randomized to intensive (randomly assigned to chlorpropamide, glibendamide, glipizide, or insulin, adjusted to keep fasting glucose < 108 mg/dl) vs. conventional (meds as needed to keep fasting glucose < 270 mg/dl or to treat symptomatic hyperglycemia) treatment.
Over median 10y f/u, median HbA1c was 7.0% in intensive group and 7.9% in conventional group.
Primary outcome defined as any of diabetes-related adverse events, including cardiac, cerebrovascular, microvascular, renal, ophthalmologic, and glycemic events. RR of primary outcome was 0.88 in intensive group (sig.); only specific outcomes that were significantly reduced were sudden death (RR 0.54), receipt of retinal photocoagulation (RR = 0.71), and cataract extraction (RR = 0.76). RR of any microvascular endpoint (renal failure, receipt of retinal photocoagulation, or vitreous hemorrhage) was 0.75 (sig.)
RR’s for DM-related death and all-cause mortality were 0.90 and 0.94 respectively; neither of the latter being significant. No differences seen in any of the endpoints based on which tx used in the intensive group. Sig. more hypoglycemic episodes and weight gain in intensive group
- "UKPDS 34"--Lancet 352:854, 1998--JW
- 1,704 overweight pts with type II DM randomized to intensive tx with metformin vs. conventional tx.
- Intensive group had sig. reduction in DM-related endpoints
- In comparison between metformin and other drugs (sulfonylureas or insulin), metformin group had fewer DM-related endpoints, less weight gain, and less hypoglycemia
- "UKPDS 35"--BMJ 321:405, 2000--JW
- 3,642 pts with newly dx'd type 2 DM randomized to intensive vs. conventional hypoglycemic Rx
- Compared subgroups of pts with final HbA1c of > 10%, 7-8%, and 6%; endpoints included any DM complication as well as DM-related death
- For all endpoints, risk was lower for lower HbA1c levels; there was no apparent "threshold" below which further lowering did not appear to be beneficial
- Diabetes Control and Complications Trial (NEJM 329:977-986, 1993)--Demonstrated reduced risk of microvascular complications
- Compared "intensive" vs. "conventional" therapy for type 1 DM & impact
on vascular & neurologic complications in 1441 pts 13-39y at enrollment
followed for mean 6.5y.- Intensive: 3 or more daily insulin injections OR insulin pump, SMBG at
least QID, target sugars 70-120 preprandial and < 180 postprandial- Conventional: 1-2 daily insulin injections
- Intensive group had sig. better glycemic control by HbA1c & mean
glucoses- Incidences of onset of new retinopathy and of progression of retinopathy were sig. lower in intensive-therapy group (relative risks (RR) 0.24 and 0.46, respectively)
- Incidence of onset of microalbuminuria wase sig. lower in intensive-therapy group (RR 0.66)
- Incidence of onset of neuropathy was sig. lower in intensive-therapy group (RR 0.31)
- Incidence of severe hypoglycemia was sig. higher in intensive-therapy group (RR 3.3)
- Incidence of reaching > 120% ideal body weight sig. increased in intensive-therapy group (RR 1.33)
- No sig. diff. in overall mortality, incidence of DKA, or quality of life (assessed through as pt questionnaire)
- Also, they did note a relationship between mean HbA1c over the course of the trial and likelihood of progression of retinopathy, such that pts with lower mean HbA1c's were less likely to have progression (defined as either onset or sig. worsening).
- Temper attempts at normoglycemia with caution to avoid hypoglycemia
- Educate re: hypoglycemic reactions (how to recognize, keep candies around)
- Glucagon for all pts on insulin
- Use of medications--see also "Oral Hypoglycemics" and "Insulin"
- Only 10% of people with Type 2 DM can achieve adequate glycemic control with lifestyle changes alone; most who can will show sig. changes within 6 wks, so give it at least that long.
- Oral agents: effective only when there is significant retained insulin secretory capacity; this is sometimes not the case in late disease.
- Switch to a different class of drug if don't reach adequate glycemic control within several weeks at maximal dosage of one drug.
- Can add Insulin to oral regimen, e.g. low-dose insulin at HS and sulfonylurea in a.m.
- Eventually may need complete insulin replacement with multiple daily injections
- Insulin vs. oral agents as initial therapy: 4,000 pts with newly diagnosed type II DM who failed dietary tx were randomized to one or the other. Insulin pts had lower fasting glucuose but no diff. in HbA1c and hypoglycemic events and weight gain more common in insulin pts (Ann. Int. med 128:165, 1998--JW)
- Medical nutrition therapy--basically just emphasizes balance between fat, CHO, and protein and not too much saturated fat
- High intake of dietary fiber improves glycemic control in diabetics
- In a randomized crossover study, 13 pts with type 2 DM at either high fiber (25g/d insoluble + 25g/d soluble) vs. moderate-fiber diet (8g/d soluble + 16g/d insoluble)--at 6wks, overall daily plasma glucose levels were 10% lower in the high-fiber group (NEJM 342:1392, 2000--JW)
- Exercise
- Weight reduction if obese
- Chromium supplementation for Diabetes Mellitus
- Chromium has been shown to increase insulin sensitivity & binding
- Chromium picolinate 1mg/d was ass'd with sig. greater decrease in HbA1c than placebo in a randomized trial of 180 pts (Diab. 46:1786, 1997--FP News 2/1/01)
- Ginseng supplementation for Diabetes Mellitus
- 9 pts with type 2 DM and 10 controls randomized to American Ginseng (Panax quinquefolius L) 3g vs. placebo 40min before a 25g oral glucose challenge test; sig. lower glucose levels in the ginseng recipients (Arch. Int. Med. 160:1009, 2000--FP News 2/1/01)
- Ginseng has been ass'd with psychiatric sx at doses > 15g/d
- Milkweed (Gymnema sylvestre)
- Uncontrolled studies done in India have suggested a hypoglycemic effect (e.g., J. Ethnopharm. 30:295, 1990 and 30:281, 1990--FP News)
- Double-blind study initiated early 2001 at Univ. of Utah
VIII. Monitoring glycemic control--"Daily monitoring is especially important for patients treated with insulin or sulfonylureas to monitor for hypoglycemia...optimal frequency [of glucose monitoring] in Type 2 diabetes is unknown"
- Home glucose monitors
- Whole blood glu levels are 10-15% lower than plasma glucose levels
- Good idea to check Qac & Qhs when changing therapy
- During stable periods, ac BIW and hs BIW are sufficient according to AAFP monograph
- Post-lunch glucose levels have greatest correlation with overal glycemic control
- 66 pts 40-78yo with type 2 DM on diet therapy or oral meds. All had plasma glucose measured x 4 on a single day--at 8am and Q3h x3. All had their usual breakfasts at 8am and their usual lunches around 12pm. Also had HbA1c checked < 10 afterward. In multiple linear regression analysis, only the "postlunch" (2pm) and "extended postlunch" (5pm) plasma glucose values were sig. ass'd with HbA1c and the correlation with HbA1c was strongest for the postlunch value. A postlunch plasma glucose < 151 was predictive of HbA1c < 7.0 and a postlunch plasma glucose < 207 was predictive of HbA1c < 8.6% ("expected values" derived from regression lines). Using these thresholds, the postlunch plasma glucose had a sensitivity of 73% and a specificity of 92% for predicting "poor control" of DM (defined as HbA1c > 8.4%). In contrast, the prebreakfast plasma glucose (8am, > 174mg/dl) was only 69% sensitive and 85% specific for predicting poor diabetic control. (Diab. Care 20:1822, 1997)
- HbA1c-reflects mean blood glucose over previous 2-3mos--ADA recc's checking at least 2x/yr in pts with stable glycemic control, more frequently in pts with change in tx or not meeting goals of glycemic control
- Glycated Serum Protein--reflects mean blood glucose over previous 1-2wks
IX. Periodic f/u care including screening in pts with type 2 DM: ADA recommends at least Q3mo visits "until achievement of treatment goals"
- Methods ok by ADA:
- Spot urine albumin-creatinine ratio (first am void preferred; 95-97% correlation with 24h albumin excretion; should be < 30ug/1mg)
- 24h urine albumin excretion
- Timed (< 24h) urine albumine excretion
- Note that ADA says you can start with standard dipstick urinalysis for protein and if positive, go straight to 24h protein excretion; albumin, which is main protein spilled in diabetic nephropathy, doesn't show up on standard urine dipsticks for protein
- Avoid screening for microalbuminuria in setting of UTI, marked HTN, severe CHF, heavy exercise, febrile illness, or recent hyperglycemia; all of these can cause transient albuminuria
- Confirm microalbuminuria with a repeat study sev. weeks later; 2 out of 3 over 3-6mos with any of the above methods considered diagnostic of microalbuminuria, consider nephrology consult if get conflicting results
- Microvascular complications tend to occur together, so nephropathy without retinopathy warrants search for other causes, e.g. NSAID
X. The Diabetes "Patient Management Plan"--a potentially useful tool in patient self-management. Items to cover:
(Sources include ADA Clinical Practice Recommendations 1998, Diab. Care 21:S1, 1/98)