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Diabetes Study Debacle: Can Fishy Nutrients Help?
2/11/2008
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Recent research highlights potential of nutrients abundant only in fatty seafood, and encourages further study

by Craig Weatherby


Last week we reported on the disappointing outcome of a major clinical trial that was designed to test the heart-health effects of lowering diabetics’ blood sugar to normal levels.


(See “Diabetes Study Shock”)


The 10,000-person study was designed to find the best way to reduce heart disease and heart attacks among long-term Type 2 diagnosed with heart disease, or with two or more other risk factors for heart disease (aside from diabetes).


Key Points

  • Failure of radical blood-sugar-lowering regimen to reduce death rates may shift focus to alternative approaches.
  • No diabetes protection found in women taking low-dose vitamin D, but prior analyses indicate higher doses may help.
  • Vitamin D exerts effects compatible with deterring or ameliorating diabetes.
  • Omega-3s reduce heart risks associated with diabetes but do not reduce blood sugar or enhance insulin sensitivity.

It compared the outcomes of treatment strategies designed to improve one of three major risk factors for heart disease among diabetics:

  1. Blood sugar levels
  2. Blood pressure levels
  3. Blood fat (triglyceride) levels

The participants assigned to the blood-sugar-lowering part of the study were further divided into “radical” and “moderate” blood-sugar-lowering groups (our characterization).


Surprisingly, the diabetics placed on the radical sugar-lowering regimen suffered a higher death rate, compared with patients placed on the more moderate regimen, which reduced their blood sugar levels but left them above normal.


Many medical observers noted that stress related to the extreme blood-sugar-lowering regimen could account for the increased death rate.


The goal for the group placed on the radical sugar-lowering regimen was to cut their levels below 6 percent on a measure called hemoglobin A1c.


(The American Diabetes Association recommends that people with Type 2 diabetes keep their blood sugar below 7 percent, which reduces patients’ risk of blood-sugar-related damage to the eyes, kidney, and nervous system.)


However, some authors of the study now say that patients with heart disease or with several risk factors should aim for levels no lower than 7 percent, rather than the near-normal 6 percent level that was the target for the radical sugar-lowering regimen.


In light of the unexpected outcome of this study, let’s take a look at recent findings about two fish-borne nutrientsvitamin D and omega-3s (EPA and DHA)in relation to diabetes.


Omega-3s in diabetes

As we’ve reported in the past, omega-3s exert effects similar to those of a major class of diabetes drugs, called glitizars, which act on cellular switches called PPARs, in ways that raise levels of HDL (“good”) cholesterol and lower blood fat (triglyceride) levels.


(See “Drug May Help Prevent Diabetes: Omega-3s Exert Comparable Effects”)


Unlike glitizar drugs, omega-3s do not enhance insulin sensitivity, which is one goal of diabetes prevention and care. Nor are the omega-3s in fish oil proven to stabilize blood sugar levels.


Last month, the authors of a comprehensive review of the medical literature summarized what’s known about the effects of supplemental fish oil in diabetes:


“Omega-3 PUFA supplementation in type 2 diabetes lowers triglycerides and VLDL [“very bad”] cholesterol, but may raise LDL cholesterol (although results were non-significant in subgroups) and has no statistically significant effect on glycemic control or fasting insulin. Trials with vascular events or mortality defined endpoints are needed.” (Hartweg J et al. 2008)


When the authors said, “Trials with vascular events or mortality defined endpoints are needed”, they no doubt were referring to two things:

  • Omega-3s improve three of the symptoms associated with diabetes: high triglyceride levels, low HDL levels, increased inflammation.
  • Omega-3s reduce cardiovascular risks associated with these diabetes symptoms: stroke, second heart attacks, and sudden cardiac death.

As they said, omega-3s do not aid blood sugar regulation or increase insulin sensitivity, so it is unlikely that fish oil can reduce the risks of nerve, kidney, or eye damage associated with diabetics’ chronically high blood sugar levels. However, omega-3s may help ameliorate the heart problems induced by diabetes (For more on this, see “Fish, Omega-3s, and Diabetes”).


Vitamin D and diabetes: Dose may be key to blood-sugar benefits

There’s some evidence that vitamin D may help discourage development of diabetes (see “Vitamin D Deters Diabetes and More: Northern Teens Deficient”).


But it appears that to enjoy this possible benefit, Americans need more dietary vitamin D than most consume.


Research published last month examined data from the Women's Health Initiative (WHI) calcium/vitamin D trial, which randomly assigned 33,951 post-menopausal women to receive daily supplements of calcium (1,000 mg) plus vitamin D3 (400 IU), or placebo pills.


After seven years of follow-up, 2,291 women were diagnosed with diabetes. And after adjusting for confounding factors, the group taking the vitamin D-calcium combination did not enjoy a reduced risk of diabetes.


However, the study’s authors acknowledged that the low dose of vitamin D the women took could explain their failure to detect any anti-diabetes benefit: “Higher doses of vitamin D may be required to affect diabetes risk...” (de Boer IH et al. 2008).


Few Americans get enough sun exposure to make optimal amounts of vitamin D in their skin, so they need to get it from foods or supplements.


The US RDA for vitamin D is 400 IU, but researchers say that most Americans need to consume 1,000 to 2,000 IU per day in order to get their blood levels high enough to help prevent osteoporosis and cancer (See “Review Supports Safety of Much Higher Vitamin D Intake”).


And it may be that by following this recommendation, people could help deter diabetes as well.


Last year, the authors of a review of the medical literature concluded that low intake of vitamin D and calcium may worsen blood sugar control, whereas taking supplements of both nutrients may help optimize blood sugar (glucose) control and glucose metabolism (Pittas AG et al. 2007)


As the Harvard-Tufts team wrote, “Evidence from trials with vitamin D and/or calcium supplementation suggests that combined vitamin D and calcium supplementation may have a role in the prevention of type 2 [diabetes]… in populations at high risk (i.e. [with] glucose intolerance)” (Pittas AG et al. 2007).


The review’s authors noted that women in the WHI whose vitamin D intake equaled or exceeded 511 IU per day had a lower risk of diabetes, compared with women whose intake was 159 IU per day or less.


They also detailed some reasons why vitamin D should help deter diabetes (Pittas AG et al. 2007):


Enhanced insulin responses

  • Vitamin D enhances function of the pancreatic beta cells that produce insulin, including the insulin response to rises in blood sugar.
  • Vitamin D may exert indirect effects via its role in regulating calcium. As they wrote, “Insulin secretion is a calcium dependent process therefore, alterations in calcium flux can have adverse effects on beta cell secretory function. We speculate that inadequate calcium intake or vitamin D insufficiency may alter the balance between the extra-cellular and intracellular beta cell calcium pools, which may interfere with normal insulin release, especially in response to a glucose load.
  • Vitamin D may enhance insulin action “…either directly, by stimulating the expression of insulin receptor… or indirectly via its role in regulating extra-cellular calcium… Results from randomized trials on the effect of vitamin D and/or calcium supplementation on insulin resistance show either no effect or improvement of insulin action with supplementation.”

Reduced inflammation

  • Diabetes is associated with systemic inflammation, which in turn has been linked to insulin resistance and death of insulin-producing beta cells. Vitamin D may improve insulin sensitivity and promote beta-cell survival by reducing the generation and effects of pro-inflammatory cytokines (immune-system messenger proteins).
  • The evidence on this score from human trials that examined the relationship between vitamin D or calcium status and systemic inflammation in relation to diabetes is, as they wrote, “limited and conflicting”, but warrants further exploration.

Diabetes is a complex disorder, with genetic as well as dietary and lifestyle influences, so it is unlikely that any drug or nutrient will be a magic bullet.


That said, it may be that some food factors might help prevent or ameliorate this epidemic disease, which is increasingly costly and debilitating to our society.


We’ll keep you updated as the evidence with regard to vitamin D, omega-3s, and diabetes accumulates.



Sources

  • de Boer IH, Kestenbaum B, Siscovick DS, Weiss NS, Tinker LF, Connelly S, Curb JD, Howard BV, Larson JC, Manson JE, Margolis KL. Calcium plus vitamin D supplementation and the risk of incident diabetes mellitus in the Women's Health Initiative. Diabetes Care. 2008 Jan 30; [Epub ahead of print]
  • Farmer A, Montori V, Dinneen S, Clar C. Fish oil in people with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2001;(3):CD003205. Review.
  • Harkness LS, Bonny AE. Calcium and vitamin D status in the adolescent: key roles for bone, body weight, glucose tolerance, and estrogen biosynthesis. J Pediatr Adolesc Gynecol. 2005 Oct;18(5):305-11. Review.
  • Hartweg J, Farmer AJ, Perera R, Holman RR, Neil HA. Meta-analysis of the effects of n-3 polyunsaturated fatty acids on lipoproteins and other emerging lipid cardiovascular risk markers in patients with type 2 diabetes. Diabetologia. 2007 Aug;50(8):1593-602. Epub 2007 May 31. Review.
  • Hartweg J, Perera R, Montori V, Dinneen S, Neil H, Farmer A. Omega-3 polyunsaturated fatty acids (PUFA) for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD003205.
  • Pittas AG, Dawson-Hughes B, Li T, Van Dam RM, Willett WC, Manson JE, Hu FB. Vitamin D and calcium intake in relation to type 2 diabetes in women. Diabetes Care. 2006 Mar;29(3):650-6.
  • Pittas AG, Lau J, Hu FB, Dawson-Hughes B. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab. 2007 Jun;92(6):2017-29. Epub 2007 Mar 27. Review.

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