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In the News: Diabetes, Dementia and Dietary Flavonoids

Higher Blood Glucose Raises Dementia Risk

Findings recently published in the NEJM echo previous reports connecting higher blood glucose levels with an increased risk of dementia in diabetes. However in this prospective, community-based cohort study (1), greater risk was observed not only in diabetics, but among non-diabetics as well.

The researchers looked at data from over 2000 patients (average age 76) who were initially free of overall dementia. Among diabetics, a 40% greater risk of dementia was seen for those with higher average blood glucose levels (190 mg/dl) vs. those with lower average levels (160 mg/dl). A nearly 20% greater risk was seen for non-diabetics with higher levels (average of 115 mg/dl vs. 100 mg/dl).  

The study was noteworthy for the extensive clinical data available (including 35,264 clinical measures of glucose levels), for the long-term follow-up of patients (median 6.8 years), and for the large number of dementia cases (524) sthat developed during the study period.

Higher blood glucose level may contribute to an increased risk of dementia through several potential mechanisms, including acute and chronic hyper-glycemia and insulin resistance, and increased small vessel disease of the brain (2).

Flavonoids May Lower risk of Type 2

A flurry of recent investigations is raising interest in the potential role of flavonoids both in diabetics and those without the disease. While flavonoids have antioxidant properties, their mechanisms of action are complex, broad, and go well beyond direct radical scavenging. There are a number of flavonoid subclasses, and even within the same subclass, individual flavonoids can differ considerably in bioavailability and bioactivity.

Substantial experimental evidence suggests that several flavonoid subclasses are involved in glucose metabolism, and three new observational studies provide evidence of this relationship in humans. The largest, a case-cohort study conducted in 8 European countries with over 340,000 participants and 12,400 incident cases of type-2, reports that higher intake of certain flavanols and flavonols (both mostly from tea and/or fruit) lowered type 2 diabetes risk (3).

In the 2nd study (4), a Tufts and Harvard team followed 2900 plus members of the Framingham Offspring cohort who were free of type 2, for a mean 11.9 years. They found that each 2.5 fold increase in flavonol intake was associated with a 26% lower incidence of type 2.

A 3rd paper5 which evaluated data from nearly 2,000 participants in the TwinsUK Study, found that higher consumption of flavones (herbs, vegetables) and anthocyanins (berries) was associated with lower insulin resistance and lower levels of the inflammatory biomarker C-reactive protein.

Results of RCTs Support Flavonoid Promise

The results of a handful of small controlled trials suggest that the observed relationship between certain flavonoid subclasses and diabetes is real. In one year- long study for example, 93 postmenopausal women with type 2 receiving flavanols (tea, chocolate) and isoflavones (soy) showed significant improvements in insulin resistance and sensitivity compared to placebo (6).

Additionally, a pair of randomized cross-over studies (7) from UK and European collaborators report that anthocyanins (blueberries) improved blood vessel elasticity (measured by flow-mediated dilation) compared to a control in 21 healthy men.

References

1. Crane PK et al. Glucose levels and risk of dementia. NEJM 369:540-8, 2013.
2. Strachan MW. The brain as a target organ in type 2 diabetes: exploring the links with cognitive impairment and dementia. Diabet Med 28:141-7, 2011.
3. Zamora-Ros R et al. Dietary intakes of individual flavanols and flavonols are inversely associated with incident type 2 diabetes in European populations. J Nutr 44:335-43, 2014.
4. Jacques PF et al. Higher dietary flavonol intake is associated with lower incidence of type 2 diabetes. J Nutr. 143:1474-80, 2013.
5. Jennings A et al. Intakes of anthocyanins and flavones are associated with biomarkers of insulin resistance and inflammation in women. J Nutr 144:202-8, 2014.
6. Curtis PJ et al. Chonic ingestion of favan-3-ols and isoflavones improves insulin sensitivity and lipoprotein status and attenuates estimated 10-year CVD risk medicated postmenopausal women with type 2 diabetes. Diab Care 35:226-232, 2012.
7. Rodriguez-Mateos A et al. Intake and time dependence of blueberry flavonoid-induced improvements in vascular function: a randomized, controlled, double-blind, crossover intervention study with mechanistic insights. Am J Clin Nutr 98:1179-91, 2013.