Start Diabetes Type 2 patients on exercise and a healthy diet with a goal of weight reduction if overweight.  A healthy diet means no mammal meat, no sugar or white flour or white flour pasta or potatoes.  Use whole grains and nuts daily.  Be sure to eat one pound of fish a week or take 2 fish oil capsules a day.  Make sure to use magnesium 250 mg twice a day and vitamin D 2000 units each day.  Women should also take calcium 500 mg twice a day.  Avoid salt.  See my nutritional recommendations for Healthy Living.

Metformin is recommended by some as an initial treatment for diabetes in view of recent British research showing a decrease in mortality.  The alternative frontline treatment is a sulfonylurea medication, e.g. glipizide.  While it has been popular to combine the two if the initial treatment didn't work, two recent studies suggest that the two combined may actually increase mortality.  Adding insulin to metformin might be a more reasonable second step and can safely and effectively begin using once-daily injections of biphasic insulin aspart 70/30, biphasic human insulin 70/30, or NPH insulin in combination with metformin (J Diabetes Complications. 2003 Nov-Dec;17(6):307-13).  Adding insulin works as well as triple drug therapy and is much less expensive for those failing two oral drugs (Diabetes Care. 2003 Aug;26(8):2238-43).

Lower blood pressure to 125/75 with enalapril (Vasotec), lisinopril or another ACE inhibitor.  Use HCTZ as a second BP medication if necessary.  If these are not successful, additional medications (clonidine is my favorite) should be used to achieve blood pressure control.

Acarbose (Precose) can help prevent complications as can a tetracycline and/or a maximum of one alcoholic drink per day (one beer or 4 ounces of wine). Acarbose costs $76 per month and is used as a secondary medication, improving blood sugar control.

Metformin can be taken only twice a day without problems although three times a day is standard.  An extended release form, Glucophage-XR, has come out but costs three times as much ($25 vs. $90).  It appears to be a waste of money for most patients. For more on metformin see metformin for obesity.

Cinnamon (1 teaspoon per day) and stevia, an inexpensive natural sweetener ( www.iherb.com ), appear to help improve blood sugar control in diabetics.  Taurine looks very good in animal studies.  It is inexpensive and 1 teaspoon a day might be a good idea. While the research is very preliminary for these two herbal approaches, they are harmless approaches.  Patients keeping careful track of their blood sugars may find a decreased need for diabetic medications or at least better control.

A recent study suggests that many should be taking a statin or possibly policosanol to help prevent heart attacks and stroke. Pioglitazone (Actos) doesn't appear of long-term benefit despite its high cost.  Sitagliptin (Januvia) is a new DPP-4 inhibitor for Type-2 diabetes ($150/month) may be useful for patients not succeeding with metformin alone.

Prevention

Metformin and Others Help Reduce Risk: A Chinese study showed that metformin and acarbose could reduce the risk of type 2 diabetes by 65 and 83% for adults with impaired glucose tolerance. The efficacy of metformin was confirmed by the Diabetes Prevention Program (31% risk reduction) and that of acarbose by the STOP-NIDDM trial (36%) in a similar high-risk population. The TRIPOD study showed that troglitazone could reduce the risk of diabetes by 55% in Hispanic women with a history of gestational diabetes. The XENDOS study showed that orlistat could reduced the risk of diabetes by 37% in obese subjects when used as an adjunct to an intensive lifestyle program. Three studies have suggested that bariatric surgery in morbidly obese subjects could reduce the risk of diabetes to near zero. A renin angiotensin aldosterone system inhibitor, as well as statin and hormone replacement therapy may also have potential benefit. Pharmacological and Surgical Intervention for the Prevention of Diabetes. Chiasson JL. Centre hospitalier de l'Universite, Montreal, Canada. Nestle Nutr Workshop 2006;11:31-42.

Treatment

Acarbose Alpha-Glucosidase Inhibitor Can Reduce Cardiovascular Events in Type 2 Diabetics: A meta-analysis of 7 DB PC studies of 2180 patients. The risk for heart attacks (HR=0.36) and any cardiovascular event (0.65, as well as glycemic control, triglyceride levels, body weight and systolic blood pressure all improved significantly. Dresden. Acarbose reduces the risk for myocardial infarction in type 2 diabetic patients: meta-analysis of seven long-term studies. Hanefeld M, Cagatay M, Petrowitsch T, Neuser D, Petzinna D, Rupp M. Eur Heart J. 2004 Jan;25(1):10-6

ACE Inhibitors & Angiotension-1 Receptor Antagonists Protect Kidney, especially in Diabetes: AASK, RENAAL, and IDNT studies all find these meds better, independent of BP control. Calcium-channel blockers should be add-ons rather than front-line hypertensive medications. No difference in mortality. Lancet 12/1/01. Ed: Captopril is the ACE inhibitor of choice due to its very low cost. 

B-12 Deficiency Anemia from Metformin Easily Treated: In a Greek study of 600 patients on metformin for an average of 12 years, 54 (9%) were found to B-12 deficient megaloblastic anemia with only 3 having parietal cell antibodies.  All quickly improved with B-12 replacement therapy. Aust Fam Physician. 2003 May;32(5):383-4. Ed: Probably still more were B-12 deficient without anemia.  All patients on metformin should take B-12 and folate supplements.

Best Treatment: For type 2 Diabetes, start with diet and exercise, add sulfonylurea if not under control (tolinase $6.30/mo, glipizide (Glucotrol) $9.60/mo, glyburide (DiaBeta/Micronase) $11.40/12.30/mo. If still not under control, add metformin or switch to Glucovance. Met Let 4/2/2001

Chromium May Help: In a small 3-month DB PC crossover study of 30 diabetics, those taking 1000 micrograms of chromium daily had their the QT interval significantly shorten from 423 milliseconds to 406. Thus, increased intake of chromium may lower cardiovascular risk in type 2 diabetic patients. Blood insulin levels decreased significantly after 3 months of chromium supplementation and this may be partly responsible for the QT interval shortening. Bojan Vrtovec et al. Ljubljana University, Slovenia. American Heart Journal, April 2005.

Chromium Helped in One of Six Studies for Prevention and One of Four for Treatment: In people at risk for diabetes, only a 1999 University of Vermont study by Cefalu found benefit from 1 mg of chromium in a very small 8-month DB study of 29 adults at high risk of diabetes. J Trace Elem Exp Med 12:71. Of four good study of people with diabetes, only one 4-month DB study found benefit from 1 mg.

Chromium: No Clear Benefit: In a very small 3-month DB PC study of 40 diabetics, those on 400 microg/d of chromium showed no benefit. Chromium supplementation does not improve glucose tolerance, insulin sensitivity, or lipid profile: a randomized, placebo-controlled, double-blind trial of supplementation in subjects with impaired glucose tolerance: response to komorowski and juturu. Gunton et al. Joslin-Harvard. Diabetes Care 28:712-713, 3/2005

Cinnamon May Be Good for Diabetics: Cinnamon's water-soluble polyphenol MHCP mimics insulin, activates its receptor, and works synergistically with insulin in cells. In a small 40-day DB PC study of 60 adult Type 2 diabetics, one, three, or six grams of cinnamon powder a day in capsules after meals of placebos were given. All responded within weeks, with blood sugar levels that were on average 20 per cent lower than a control group. Some even achieved normal blood sugar levels. It also lowered blood levels of triglycerids 23-30% and "bad" LDL cholesterol 7-27%, which are also partly controlled by insulin. No significant HDL cholesterol change occurred. In test tube experiments, it neutralized free radicals. Cinnamon improves glucose and lipids of people with type 2 diabetes. Khan A, Safdar M, et al. Peshawar, Pakistan. Diabetes Care. 2003 Dec;26(12):3215-8. One gram works fine and research is being done on smaller amounts. (I have found cinnamon in 2006 for just $1.70 for 7 oz. or  less than 1 cent per day).

Cinnamon No Help for Diabetics: In a smaller Dutch study of 13 diabetic women, 1.5 g (3/4 teaspoon) per day for six weeks had no impact of a glucose tolerance test vs. similar women given placebo. J Nutr I136:977, 2006. This study is half the size and with a smaller amount.

Cinnamon extract Prevents the Insulin Resistance induced by a high-fructose diet in Rats: Qin B, et al. Nagoya University, Japan. Horm Metab Res. 2004 Feb;36(2):119-25. Cinnamon raises HDL in rats. J Med Food. 2003 Fall;6(3):183-91. Of the dried culinary herbs tested, oregano, sage, peppermint, thyme, lemon balm, clove, allspice and cinnamon all contained very high concentrations of antioxidants. J Nutr. 2003 May;133(5):1286-90

Coccinia May Help: Coccinia indica is a creeper which grows wildly in Bangladesh and India. The plant has been used since ancient times as an antidiabetic drug in Ayurvedic medicine. In a 6-week 32-patient DB PC study, of 16 diabeticsgiven , 10 showed marked improvement in their glucose tolerance while none out of the 16 patients in the dummy group showed such a marked improvement. This difference is highly significant (kappa 2 with Yates' correction = 11.7, P < 0.001). Coccinia indica in the treatment of patients with diabetes mellitus. Azad Khan AK, Akhtar S, Mahtab H. Bangladesh Med Res Counc Bull. 1979 Dec;5(2):60-6

CoQ10 Helped in Very Small Study: In a 12-week DB PC study of 40 diabetics, Coenzyme Q10 200 mg/day lower glycated hemoglobin. Eur J Clin Nutr 56:1137, 2002. This is far too little data to prove anything.

Diabetes Lowered by Magnesium in Diet in Three Huge Studies: Long-term Harvard studies of 85,060 women and 42,872 men who had no history of diabetes, cardiovascular disease, or cancer at baseline with 18 years of follow-up in women and 12 years in men found 4,085 and 1,333 incident cases of type 2 diabetes, respectively. After adjusting for age, BMI, physical activity, family history of diabetes, smoking, alcohol consumption, and history of hypertension and hypercholesterolemia at baseline, the relative risk (RR) of type 2 diabetes was 0.66 in both groups, comparing the highest with the lowest quintile of total magnesium intake. The RRs remained significant after additional adjustment for dietary variables, including glycemic load, polyunsaturated fat, trans fat, cereal fiber, and processed meat in the multivariate models. The inverse association persisted in subgroup analyses according to BMI, physical activity, and family history of diabetes. Major food sources of magnesium, such as whole grains, nuts, and green leafy vegetables. Magnesium intake and risk of type 2 diabetes in men and women. Lopez-Ridaura R, Willett WC, Rimm EB, Liu S, Stampfer MJ, Manson JE, Hu FB. Diabetes Care. 2004 Jan;27(1):134-40. 

E. Littorale Claimed of Benefit: Mamijava (Enicostemma littorale) is a glabrous perennial herb. Traditionally it is used as a stomachic and bitter tonic.  I have found it for sale only as a part of an Ayurvedic concoction of 10 herbs promoted for blood sugar control. An apparently open trial 3-month study of 84 diabetics in India reported reduced blood glucose and reduced serum insulin levels as well as prevention of the progression of complications in diabetic patients. Significant improvement in kidney function, lipid profile and blood pressure was also claimed. Efficacy of Enicostemma littorale in type 2 diabetic patients. Upadhyay UM, Goyal RK. Phytother Res. 2004 Mar;18(3):233-5. Ed: Little confidence should be placed in this study. Hopefully, better controlled studies will soon be reported.

Diabetes Gestational Type: Post-Partum Depression Increased; Treating Diabetes Lessens: In a follow-up random assignment study of 1000 women with diabetes developing gestational diabetes, i.e., diabetes during pregnancy which usually goes away after delivery, half with women had repeated blood sugar testing and counseling on diet. One-fifth received insulin as well. Half the women weren't told they had gestational diabetes and received only routine care. Three women in the untreated group had stillbirths and two newborns died vs. none with treatment. Half as many infants of the treated group weighed over 8.8 pounds. Only 1% of the treated vs. 4% of untreated had complications. Post-partum depression occurred in half as many of the treated women. CG Solomon, Brigham & Women's-Harvard. 6/16/05 NEJM. 

Ginseng Helps in One Study: In an 8-week DB PC study of 36 Type 2 patients with ginseng (100 or 200 mg) or placebo, ginseng elevated mood, improved psychophysical performance, and reduced fasting blood glucose (FBG). The 200-mg dose of ginseng improved glycated hemoglobin, and physical activity. Ginseng therapy in non-insulin-dependent diabetic patients. Sotaniemi EA, Haapakoski E, Rautio A. University of Oulu, Finland. Diabetes Care. 1995 Oct;18(10):1373-5. In a much lower quality study, single doses of cultivated American ginseng to 19 diabetics and 32 non-diabetics of 1-9 g helped blood glucose return to normal levels more quickly than in the same people with placebo. Vuksan et al. Univ Toronto. J Am Coll Nutr 19:738, 2000. However, single doses of Asian ginseng raised blood glucose in non-diabetics and other types had no benefit. J Am Coll Nutr 23:248, 2004. 

Glitazone Prevented Diabetes Type 2 in Women with Gestational DM: 121 young Latinas with recent gestational diabetes troglitazone or a placebo. It helps the body's cells more effectively use insulin to absorb glucose. FDA recalled troglitazone in 2000. USC researchers switched to prescribing pioglitazone, a similar-acting, FDA-approved drug. decline in beta-cell function of 30 percent during the time they were developing diabetes while taking placebo. Once they developed diabetes and started taking the drug, the beta-cell decline stopped. When the body's muscle and fat cells grow resistant to insulin, the beta cells in the pancreas shift into overdrive to produce more insulin to compensate. Over time, this high workload causes beta cells to wear out. ADA Session 6/02. Glitazone induces production of glycerol kinase which stores fatty acids in fat cells, increasing weight while simultaneously increasing insulin sensitivity. Glycerol kinase recombines fatty acid and glycerol for storage as triglycerides, and also increase fat cell uptake of fatty acids. U Penn Nature Medicine 9/25/02

Glucovance: New combo of glyburide and metformin at 1.25/250 ($59), 2.5/500 ($70), and 5/500 ($70) for twice daily dosing up to two BID with meals. Lactic acidosis from metformin means don’t use it for elderly or those with renal insufficiency. Metformin enhances liver and muscle insulin sensitivity. Glyburide, a sulfonyurea, increases endogenous insulin sensitivity and can cause hypoglycemia. Both can be better than either alone for type 2. Cheaper and more convenient but better start with just one drug. Med Let 2000. For glipizide, start 5 mg 30 min. before breakfast and increase if needed. Add metformin if needed. 

Herbal Remedies: It is estimated that more than 200 species of plants exhibit hypoglycaemic properties, including many common plants, such as pumpkin, wheat, celery, wax guard, lotus root and bitter melon. Phytother Res. 2003 Dec;17(10):1127-34. A total of 108 trials examining 36 herbs (single or in combination) and 9 vitamin/mineral supplements, involving 4,565 patients with diabetes or impaired glucose tolerance, were analyzed, including 58 controlled clinical trials involving individuals with diabetes or impaired glucose tolerance (42 randomized and 16 nonrandomized trials). Most involved patients with type 2 diabetes. Heterogeneity and the small number of studies per supplement precluded meta-analyses. Of the 58 trials, the direction of the evidence for improved glucose control was positive in 76% (44 of 58). Very few adverse effects were reported. While adequate evidence does not exist for any supplement, the best evidence for efficacy from adequately designed randomized controlled trials is available for Coccinia indica and American ginseng. Chromium has been the most widely studied supplement. Other supplements with positive preliminary results include Gymnema sylvestre, Aloe vera, vanadium, Momordica charantia, and nopal. Systematic review of herbs and dietary supplements for glycemic control in diabetes. Yeh GY, Eisenberg DM, Kaptchuk TJ, Phillips RS. Harvard. Diabetes Care. 2003 Apr;26(4):1277-94. More recent studies include a well-controlled study with cinnamon and a very inadequate study of E. littorale, both of which are noted above.  I do recommend cinnamon and the use of stevia as a sweetener.

Hypertension: Treatment of High Blood Pressure Lowers Diabetes Damage: Of 950 diabetics in a DB 5 year study assigned to have blood pressure lowered to either 137/81 or 125/75, the lower level reduced strokes by one-third and less loss of sight and kidney failure. U Colo, 4/26/02.

Inhaled Insulin Only Better than Metformin for Most Out-of-Control: In a randomized open-label 24-week trial adding inhaled human insulin (INH; Exubera) or metformin to sulfonylurea monotherapy in patients with poorly controlled type 2 diabetes. in the A1C >9.5% patients, INH demonstrated a significantly greater reduction in A1C than metformin (-2.17 vs. -1.79%). In the A1C < or =9.5% patients, there was no difference (-1.94 vs. -1.87%). Hypoglycemia (events/subject-month) was greater with INH (0.33) than with metformin (0.15). An open, randomized, parallel-group study to compare the efficacy and safety profile of inhaled human insulin (Exubera) with metformin as adjunctive therapy in patients with type 2 diabetes poorly controlled on a sulfonylurea. Barnett AH, et al. University of Birmingham, UK. . Diabetes Care 2006 Jun;29(6):1282-7. 

Insulin: Inhaled Exubera Insulin No Better than Regular Insulin: Despite its high $200 per month cost, Exubera did no better when combined with long-acting ultralente vs. two daily injections of NPH/regular insulin. It did do better for type 2 diabetes not adequately controlled by oral meds when compared to oral meds alone, but NPH or NPH/regular would very likely have done just as well. Diabetes Care 200528:1922; Diabetes Care 2004;27:2356.

Insulin: Long-Acting Levemir (Detemir) No Better than NPH: The more expensive Levemir ($78/1000 units) did not better than Humulin N or Novolin N ($32) in improving glycemic control as measured by HbA1c in two studies with Type 1 and two studies with type 2 diabetes. 

Kothala Himbutu Tea Said to Help Diabetes: In a 6 month DB PC crossover study of 51 stable type II diabetics being treated with exercise, diet, medication, and lifestyle modification, an herbal tea containing Salacia reticulata (Kothala Himbutu tea) for three months results in the HbA(1)C being significantly lower (6.29 versus 6.65; P=0.008). A statistically significant fall in HBA1c was seen with the active tea compared to a rise in HbA(1)C with the placebo tea (0. 54 versus -0.3; P<0.001). The daily mean dose of Glibenclamide fell by 1.89 mg in the drug treated group but rose by 2.25 mg in the placebo treated group (P=0.07). The differences in the metformin dose were not significantly significant in the two groups. We conclude that Kothala Himbutu tea is an effective and safe treatment for type 2 diabetes. A double blind randomised placebo controlled cross over study of a herbal preparation containing Salacia reticulata in the treatment of type 2 diabetes. Jayawardena MH, de Alwis NM, et al. University of Sri Jayawardanapura, Sri Lanka. J Ethnopharmacol. 2005 Feb 28;97(2):215-8.

Lipoic Acid Helped in Very Small Study: In a very small German study of 55 diabetics gien lipoic acid at 600, 1200, or 1800 mg/day for 4 weeks, insulin resistance was lower than in 19 given placebo. Free Radical Bio Med 27:309, 1999. This is far too little data.

Magnesium in Diet Prevented Diabetes in Three Huge Studies: Long-term Harvard studies of 85,060 women and 42,872 men who had no history of diabetes, cardiovascular disease, or cancer at baseline with 18 years of follow-up in women and 12 years in men found 4,085 and 1,333 incident cases of type 2 diabetes, respectively. After adjusting for age, BMI, physical activity, family history of diabetes, smoking, alcohol consumption, and history of hypertension and hypercholesterolemia at baseline, the relative risk (RR) of type 2 diabetes was 0.66 in both groups, comparing the highest with the lowest quintile of total magnesium intake. The RRs remained significant after additional adjustment for dietary variables, including glycemic load, polyunsaturated fat, trans fat, cereal fiber, and processed meat in the multivariate models. The inverse association persisted in subgroup analyses according to BMI, physical activity, and family history of diabetes. Major food sources of magnesium, such as whole grains, nuts, and green leafy vegetables. Magnesium intake and risk of type 2 diabetes in men and women. Lopez-Ridaura R, Willett WC, Rimm EB, Liu S, Stampfer MJ, Manson JE, Hu FB. Diabetes Care. 2004 Jan;27(1):134-40. The Women's Health Study of 39,345 women followed for six years reported similar findings. Diabetes Care. 2004 Jan;27(1):59-65.  Ed: I recommend a magnesium supplement of 250-500 mg/day in addition to the amount in a standard multivitamin with minerals. Its great stuff.

Magnesium Levels Strongly Associated with Lower Diabetes Type 2: In a 6 year follow-up of 12,000 men, researchers found the sextile (1/6) with the highest blood magnesium had half the level of diabetes as that with the lowest level although there was no measurable impact found based on reported dietary intake. Johns Hopkins. Arch Intern Med 1999 Oct 11;159

Magnesium Supplementation Helps Diabetes Type 2: In a DB PC study of 63 diabetes, magnesium supplementation lowered glucose, HbA(1c) (8.0 vs. 10.1), and increased insulin sensitivity. Oral Magnesium Supplementation Improves Insulin Sensitivity and Metabolic Control in Type 2 Diabetic Subjects: A randomized double-blind controlled trial. Rodriguez-Moran M, Guerrero-Romero F. Diabetes Care. 2003 Apr;26(4):1147-52 

Magnesium: However, refined grains, glycemic index, fruits and vegetables had no impact. Prospective 6 year follow-up Iowa study of 36,000 women. Am J Clin Nutr 2000 Apr;71(4):921-30

Magnesium Helps Insulin Resistance in Pre-Diabetics: In a 3-month DB PC study of non-diabetic insulin resistant subjects with hypomagnesemia (<0/74 mmol/l) using magnesium chloride (MgCl2) 2.5 g daily, magnesium-supplemented subjects significantly increased their serum magnesium levels (0.61 to 0.81 mmol/l, p<0.0001) and reduced insuliin resistance hypoHOMA-IR index (4.6 to 2.6, p<0.0001), whereas control subjects did not. A double-blind placebo-controlled randomized trial. Guerrero-Romero F, Tamez-Perez H, Gonzalez-Gonzalez G, Salinas-Martinez A, Montes-Villarreal J, Trevino-Ortiz J, Rodriguez-Moran M. Mexico. Diabetes Metab. 2004 Jun;30(3):253-8 

Magnesium: Magnesium Helped Diabetics in Very Small Study: Magnesium 300 mg/day in the form of mineral water was given to nine mild type 2 diabetic patients for 30 days. Fasting serum immunoreactive insulin level decreased significantly ( p < 0.05). There was a marked decrease of the triglyceride levels after supplementation. The patients with hypertension showed significant reduction of systolic (p < 0.01), diastolic (p = 0.0038), and mean (p < 0.01) blood pressure. Clinical efficacy of magnesium supplementation in patients with type 2 diabetes. Yokota K, Kato M, et al. Jikei University, Japan. J Am Coll Nutr. 2004 Oct;23(5):506S-509S

Magnesium: In a 4-year follow-up study of 36,787 adults ages 40-69 without diabetes, 365 developed diabetes. The odds ratio (OR) for the highest fourth in consumption of white bread vs. the lowest was 1.37 (P = 0.001), intake of carbohydrate (OR per 200 g/day 0.58), sugars (OR per 100 g/day 0.61), and magnesium (OR per 500 mg/day 0.62) were inversely associated with incidence of diabetes, whereas intake of starch (OR per 100 g/day 1.47) and dietary Glycemic Index (OR per 10 units 1.32) were positively associated with diabetes. These relationships were lessened by adjustment for BMI and waist-to-hip ratio. Glycemic index and dietary fiber and the risk of type 2 diabetes. Hodge AM, English DR, et al. Melbourne, Australia. Diabetes Care. 2004 Nov;27(11):2701-6 

Metformin Treatment of Choice Type 2 Overweight: type 2 diabetes randomized to intensive treatment with metformin, sulphonylurea, or insulin had similar degrees of glycemic control and significantly reduced microvascular end points. The study showed that the use of metformin in obese patients reduced cardiovascular events. The group treated with metformin had no hypoglycaemia and less weight gain. Treatment with metformin rather than diet alone produced a significant reduction in relative risk in all cause mortality (36%, P=0.011), diabetes related deaths (42%, P=0.017), any diabetes related end point (32%, P=0.0023), and myocardial infarction (39%, P=0.01). Metformin is the only oral hypoglycaemic agent proved to reduce cardiovascular risk and is now recognized as the treatment of choice in overweight patients with type 2 diabetes. Contraindications to the use of metformin, G C Jones, J P Macklin, and W D Alexander, BMJ 2003; 326: 4-5; Suggested contraindications: Stop if serum concentration of creatinine is higher than 150 micromols/l.* Withdraw during periods of suspected tissue hypoxia (for example, due to myocardial infarction, sepsis). Withdraw for three days after contrast medium containing iodine has been given, and start treatment with metformin only after renal function has been checked. Withdraw two days before general anesthesia and reinstate when renal function is stable.

Metformin Extended Release Compared: Adults with type 2 diabetes (newly diagnosed, treated with diet and exercise only, or previously treated with oral diabetic medications) were randomly assigned to receive one of three extended-release metformin treatment regimens (1,500 mg/day q.d., 1,500 mg/day twice daily, or 2,000 mg/day q.d.) or immediate-release metformin (1,500 mg/day twice daily) in a double-blind 24-week trial. The mean changes from baseline to end point in the two groups given 1,500 mg extended-release metformin (-0.73 and -0.74%) were not significantly different from the change in the immediate-release metformin group (-0.70%), whereas the 2,000-mg extended-release metformin group showed a greater decrease in A1C levels (-1.06% vs.-0.70%). Fewer patients in the extended-release metformin groups discontinued treatment due to nausea during the initial dosing period than in the immediate-release metformin group. Efficacy, tolerability, and safety of a novel once-daily extended-release metformin in patients with type 2 diabetes. Schwartz S, et al. San Antonio, Texas, USA. Diabetes Care 2006 Apr;29(4):759-64.

Metformin Helped DM Type 2 Insulin Patients: In a 12-month DB PC study of 183 patients with Type 2 diabetes on maximum tolerated oral agents referred for insulin conversion, those given metformin up to 2 g a day or maximum tolerated dose in addition to insulin had less weight gain [6.1 kg vs. 7.6 kg; P = 0.02], a greater reduction in HbA(1c)[1.5% vs. 1.3%; P = 0.02] and a lower insulin requirement [62 units vs. 86; P < 0.001], but 24% more hypoglycaemia [P = 0.03]. Treatment satisfaction improved more in patients on metformin than on placebo (P < 0.001), as did the positive well-being score (P = 0.02). Metformin should be continued in patients with Type 2 diabetes who transfer to insulin. Continuing metformin when starting insulin in patients with Type 2 diabetes: a double-blind randomized placebo-controlled trial. Douek IF, Allen SE, et al. University of Bristol, UK. Diabet. Med. 22, 634-640 (2005).

Metformin Lowers Cancer Risk in Diabetics by 25%: In a DB PC study of 6,000 diabetic adults, the half assigned to take metformin developed 25% fewer cases of cancer during follow-up. The metformin simulates an enzyme AMPK which may keep cancer at bay. Metformin lowers insulin-like growth factor, which in higher levels has been linked to prostate, breast, and colon cancers. Metformin is currently being investigated as a general cancer preventive agent. Alessi et al. University of Dundee, BMJ  7/2005.

Metformin No Increase in Lactic Acidosis: A meta-analysis covering 56,000 patients in Archives of Internal Medicine 11/24/03 found no evidence that metformin increased the risk of lactic acidosis. For type 2 diabetes mellitus, it has been shown to reduce total mortality rates compared with other antihyperglycemic treatments but was thought to increase the risk of lactic acidosis. Shelley R. Salpeter, Stanford University 

Oral Hypoglycemics: Diabetes Causes Mental Impairment in Senior Citizens; Treatment Helps: In a study of 18,999 ex-nurses in Boston ages 70-81, women with diabetes were at 25-35% more likely to do poorly on cognitive testing.  Odds of poor cognition were particularly high for women who had had diabetes for a long time (over 14 years) (1.52). In contrast, women with diabetes who were on oral hypoglycaemic agents performed similarly to women without diabetes, while women not using any medication had the greatest odds of poor performance (1.71) compared with women without diabetes. Prospective study of type 2 diabetes and cognitive decline in women aged 70-81 years. Giancarlo Logroscino. BMJ  2004;328:548 (6 March) 

Pioglitazone (Actos) No Long-Term Benefit in Large Study: Pioglitazone in the 3-year Proactive study of 5238 patients with type-2 diabetes did not improve the major endpoint of death, heart attack, stroke, or amputation. Med Letter 1/30/06. The authors of the study claimed a very small benefit.

Pynogenol Helped Diabetes a Little: In a DB PC study of 77 diabetes type II patients of the French maritime pine bark extract, Pynogenol(R) 100 mg for 12 weeks, during which a standard anti-diabetic treatment was continued, the supplement significantly lowered plasma glucose levels as compared to placebo. HbA1(c) was also lowered, but this was statistically significant only for the first month. In the Pycnogenol(R)-group endothelin-1 was significantly decreased, while 6-ketoprostaglandin F(1a) in plasma was elevated compared to placebo. Nitric oxide levels in plasma increased during treatment in both groups, but, differences did not reach statistical significance. Pycnogenol(R) was well-tolerated with ECG, electrolytes, creatinine and blood urea nitrogen remaining unchanged in both groups. Mild and transient unwanted effects were reported for both groups without significant differences. Antidiabetic effect of Pycnogenol(R) French maritime pine bark extract in patients with diabetes type II. Liu X, Wei J, Tan F, Zhou S, Wurthwein G, Rohdewald P. Beijing, PR China. Life Sci. 2004 Oct 8;75(21):2505-13

Sitagliptin Helped in Type-2: In a manufacturer-funded 18-week DB PC study of 521 type-2 patients ages 27-76 with a mean baseline HbA(1c) of 8.1%, sitagliptin 100 mg once daily reduced the HbA(1c) by 0.6% more than placebo, while sitagliptin 200 mg once daily reduced it 0.48%. The incidence of hypoglycaemia and gastrointestinal adverse experiences was not significantly different between sitagliptin and placebo. Sitagliptin had a neutral effect on body weight. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus. Raz I, et al. Hadassah University Hospital, Jerusalem, Israel. Diabetology 2006 Nov;49(11):2564-71.

Statin Helps Diabetics as Primary Prevention: In the DB PC CARDS study of 2,838 UK type 2 diabetics with no history of CVD, low-density lipoprotein (LDL) levels of 160 mg/dL or lower, triglyceride levels of 600 mg/dL or lower, and at least one of the following risk factors: hypertension, retinopathy, microalbuminuria, macroalbuminuria, or smoking, 25% of patients had LDL cholesterol levels less than 100 mg/dL. Those who received 10 mg daily of atorvastatin had a 37% reduction in major cardiovascular events such as acute myocardial infarction, stroke, angina, and revascularization compared with control patients. In all, 48% fewer patients in the atorvastatin group than in the placebo group suffered strokes, and all-cause mortality was 27% lower. During the course of the study, about 9% of patients who were in the placebo group originally started taking a statin. In the atorvastatin group overall about 15% of patients stopped taking atorvastatin and weren't taking any other statin either. This means the results are probably an underestimate of the real effect. ADA 64th Annual Scientific Sessions: Abstract 15-LB. June 6, 2004 

Stem Cells Changed to Islet Cells: intestinal hormone called glucagon-like peptide-1 (GLP-1) can provoke beta cells to proliferate and to secrete insulin. Habener and his laboratory now provide evidence that the hormone may also cause islet stem cells to differentiate, or mature, into true beta cells. In a 2001 study, the team identified the islet stem cells called nestin-positive islet-derived progenitor cells (NIPs) and showed that NIPs could develop into insulin-secreting cells. MGH, Endocrinology 8/02. NIPs express a receptor protein that binds to GLP-1 and, when activated, induces the NIPs to differentiate into insulin-secreting cells.

Stevioside May Be Good for Diabetics: Stevioside, a sweetener from a South American plant, has been used for the treatment of diabetes in Brazil. In a DB PC crossover study of a single dose of 1 g (1 teaspoon) of stevioside with a standard meal, type 2 diabetic patients, stevioside reduced the incremental area under the glucose response curve by 18% (P =.013). The insulinogenic index (AUC(i,insulin)/AUC(i,glucose)) was increased by approximately 40% by stevioside compared to control (P <.001). Stevioside tended to decrease glucagon levels, while it did not significantly alter the area under the insulin, glucagon-like peptide 1, and glucose-dependent insulinotropic polypeptide curves. Thus, stevioside reduces postprandial blood glucose levels in type 2 diabetic patients, indicating beneficial effects on the glucose metabolism and for type 2 diabetes. Antihyperglycemic effects of stevioside in type 2 diabetic subjects. Gregersen S, Jeppesen PB, Holst JJ, Hermansen K. Aarhus University Hospital, Denmark. Metabolism. 2004 Jan;53(1):73-6. Rat studies also find both anti-hypertensive and anti-hyperglycemic effects from stevioside. Metabolism. 2003 Mar;52(3):372-8.

Tetracyclines Helpful: AAAS 2001 meeting reported tetracyclines decrease periodontal and cancer. Golub of SUNY Stony Brook found diabetes fosters the breakdown of collagen, the structural protein in bone and connective tissue via colleganases. Tetracyclines protect collagen even in animals without periodontal germs by disarming collagenase although other antibiotics didn’t work. It was effective well below killing dose. It also slows osteoporosis. Tetracyclines help periodontal disease in diabetes. Decreases cytokines e.g. interleukin-1 beta inflammatory compound which also decrease insulin’s action. Use in treating AODM. Prevented cataracts, wasting, and impaired wound healing in animals with diabetes. It thwarts angiogenesis. Helped Kaposi’s sarcoma with a 50% response rate in advanced cases and may help prostate CA. (Sci News 2/24/01)

Tight Control No Impact on Death; Metformin, Hypertension Control Does: Only six of the reviews included the patient oriented information that tight blood glucose control had no effect on diabetes related or overall mortality. Just seven mentioned that metformin treatment was associated with decreased mortality. Most (30) of the reviews did not report that diabetic patients with hypertension benefit more from good blood pressure control than good blood glucose control. No review pointed out that treatment of overweight patients with type 2 diabetes with insulin or sulphonylurea drugs had no effect on microvascular or macrovascular outcomes. Thirteen reviews recommended drugs as first line treatment for which we do not have patient oriented outcomes data. The average validity assessment score was 1.3 out of a possible score of 15. What happened to the valid POEMs? A survey of review articles on the treatment of type 2 diabetes. Allen F Shaughnessy, associate director¹, David C Slawson, BMJ 8/2/03

Tight Control in Type 2 Reduces Complications: Keeping BP and HbA-1c normal reduces complications. BMJ 8/12/00. 5% of Type 2 found hereditary. USA Today 9/27/00.

Thioctic Acid Might Help: In a DB PC study, thioctic acid at an oral dosage of 800 mg/day for 4 months significantly improved cardiac autonomic neuropathy in type 2 diabetic patients. Treat Endocrinol. 2004;3(1):41-52.

Ulcer Treatment Regranex Very Expensive and of Small value: Becaplermin = recombinant human platelet-derived growth factor gel applied topically. In 20 wk DB 48% vs. 25% ulcers healed with 30% recurrence. $378 for 3 week treatment Med Letter 7/17/98.

Urinary Tract Infections Increased by Diabetes Meds: In a case-control study of 901 cases of urinary tract infections and 913 controls, diabetes was reported in 13.1 and 6.8%. The age-adjusted odds ratio (OR) for UTI for diabetes was 2.2. Adjustment for frequency of sexual intercourse and history of UTI had little effect. Compared with nondiabetic women, higher UTI odds were seen in subjects who used oral hypoglycemic agents (OR 2.9) and insulin (2.6) but not in subjects with untreated diabetes or diabetes treated by lifestyle changes (1.3). Diabetes and the risk of acute urinary tract infection among postmenopausal women. Boyko EJ, Fihn SD, Scholes D, Chen CL, Normand EH, Yarbro P. Diabetes Care. 2002 Oct;25(10):1778-83

Vitamins B-1 & B-6 Help Diabetic Peripheral Neuropathy: DB PC 200 thiamine 25mg/d and pyridoxine 50mg/d. 49% vs. 11% decrease. Evaluation of the efficacy of thiamine and pyridoxine in the treatment of symptomatic diabetic peripheral neuropathy. Abbas ZG, Swai AB. East Afr Med J 1997 Dec;74(12):803-8

Vitamin C May Help Diabetes: An inverse association was found between plasma vitamin C and HbA1c. Dietary measures to increase plasma vitamin C may be an important public health strategy for reducing the prevalence of diabetes. Diabetes Care 2000 Jun;23(6):726-32

Vitamin E 1200 IU Protects Against DM Chronic Infection: The University of Texas Southwestern studied 47 Type 2 Diabetics and 25 healthy adults giving them 1200 IU/day for 3 months. Half of the diabetics had had major complications, e.g. kidney failure and had higher CRP (C-reactive Protein), a marker of inflammation. CRP down dramatically in all 3 groups. Interleukin-6 (this cytokine tells liver make CRP) levels after WBC stimulation only one-third as high. Free Radical Biol 10/23/00. DM WBC’s secrete 3 substances that foster atheroscl and Vit E dramatically reduced all three. Circ 7/11/00.

Vitamins E 680 IU, and C 1250 mg Reduce Albuminuria in Diabetes: Double-blind, randomised study of the effect of combined treatment with vitamin C and E on albuminuria in Type 2 diabetic patients. Gaede P, Poulsen HE, Parving HH, Pedersen O. Diabet Med 2001 Sep;18(9):756-60. Ed: Vitamin E has been called into question recently.

Drugs Stop VEGF DM/Wet Macular Degen Blindness: rhuFab zeroes in on a growth-promoting protein called vascular epidermal growth factor, or VEGF. Excessive blood vessel growth which ooze fluids on retina cause both types of blindness. Dry MD more common, slower, and not helped. Must be given soon after symptoms start. Other drugs: Anecortave acetate, a new steroid injected next to the eye once every six months for macular degeneration. Eyetech Pharmaceuticals' EYE001, which is injected into the eyeball like rhuFab for macular degeneration. Bausch & Lomb's Retisert implant, which exudes a steroid into the eye for up to three years and is being used for diabetic retinopathy and macular degeneration. CNN 7/2/02

Insulin Inaction Hurts Nondiabetics: People without diabetes may have insulin resistance with up to 1/3 of adults facing this risk. Triggers more insulin production which damages blood vessels with tripling of oxidation of fatty substances in blood. They have far lower antioxidants. More research needed to find cause-effect. Am J Clin Nutr 9/00.

Rosiglitazone (Avandia) Can Decrease HDL: Rosiglitazone (Avandia) may rarely cause a profound decrease in high-density lipoprotein (HDL) "good" cholesterol and an increase in fasting triglycerides.  Three patients with type 2 diabetes and high cholesterol are reported in whom treatment with rosiglitazone was temporally related to a sharp decline in blood levels of HDL cholesterol. The patients had a rapid return of HDL cholesterol to pretreatment levels when the drug was stopped.  Despite this abnormal cholesterol response, all three patients experienced "striking improvement" in blood sugar control with rosiglitazone treatment. Anita Sarker, et al. Cambridge, UK, Diabetes Care, November 2004.

Vanadium in High Doses Helped in Small Studies But Dangerous: Four small studies of just 37 diabetics for 20-30 mg/day of vanadium helped, but this is 10 times the recommended upper limit (1.8 mg/d). Animal research shows high doses can damage the kidneys. Metabolism 49:400, 2000. 

Thomas E. Radecki, M.D., J.D.

 modern-psychiatry.com