Type 2 diabetes is increasingly common in industrially developed societies. Simon Mills explores the onset and management of Type 2 diabetes.
Type 2 or late-onset diabetes, marked by persistently high levels of glucose in the blood, is increasingly common in industrially developed societies. It is also rocketing in countries which have been industrialising most rapidly (e.g. India and China). It has been linked to excessive food intake, especially carbohydrate and sugar consumption, and a reduction in exercise. It is particularly associated with obesity and cardiovascular disease.
There are serious health complications of diabetes, especially if not controlled. There is a greater risk of cardiovascular disease and dementia, and in severe cases, of kidney disease, blindness and amputations. The World Health Organization (WHO) reports that diabetes is one of the leading causes of death in the world, and rapidly increasing in its impact.
Fortunately most cases of Type 2 diabetes can be controlled by diet and exercise, and particularly by weight loss. There are likely to be added benefits with incorporating plant foods, spices and supplements into the diet. We will look at these opportunities.
Firstly we can consider five ways to address the onset and management of Type 2 diabetes.
Pre-diabetic syndrome
Type 2 diabetes mellitus is most often preceded and is accompanied by an increasing resistance to the action of insulin in moving glucose from the blood into the cells. This condition has been referred to as metabolic syndrome, insulin resistance syndrome, or syndrome X. It is a disorder of energy utilisation and storage, diagnosed by a co-occurrence of three out of five of the following medical conditions:
- Abdominal (central) obesity
- Elevated blood pressure
- Elevated fasting plasma glucose
- High serum triglycerides
- Low high-density cholesterol (HDL) levels
Metabolic syndrome increases the risk of developing cardiovascular disease, particularly heart failure, and diabetes itself. Some studies have shown the prevalence in the UK to be over a third of the adult population (1) and this increases with age.
We will see there are a number of ways in which we can use plants to reduce insulin resistance.
Insulin resistance and the microvasculature
An immediate impact of increased insulin resistance is on the integrity of the endothelium, the cell wall lining of the blood vessels, and the single interface between blood and tissues at the capillaries.
The endothelium is the frontline in inflammation: this is where the white blood cells are activated and switch on inflammatory cytokines and other initiators. Many long-term complications of diabetes can be laid directly to the direct inflammatory pressures of insulin resistance.
Endothelial dysfunction leads to the following:
- Increased vascular endothelial growth factor (VEGF)
- Capillary basement membrane thickening
- Increased inflammatory cell adhesion
- Increased leptin and inflammatory adipocytokines (from increased fatty tissue)
- Increased inflammatory activity and cytokine concentrations
- Yet more insulin resistance
This in turn leading to the following pathological developments:
- Oxidation-induced reduction in vasodilation
- Reduced tissue perfusion and hypoxia
- Impaired tissue oxidation – fatty infiltration and its pathological consequences
- Adiposity
There was a recent dramatic illustration of the importance of this endothelial interface in early observations of the incidence of severe complications of Covid-19: that these were associated with health conditions (obesity, cardiovascular disease, diabetes) associated with insulin resistance and endothelial dysfunction.
We will see that there are promising plant based approaches to improving endothelial function.
Vascular complications of diabetes
The most distressing consequences of poorly managed diabetes follow from endothelial dysfunction and disruption in blood supply.
Retinopathy: Damage to capillary blood supply to the retina, with the development of microaneurysms, retinal haemorrhages, and exudates; this progresses to a ‘proliferative’ phase with the presence of new blood vessels. Blindness is a possible outcome.
Nephropathy: A persistent proteinuria which can progress to a decline in renal function and end-stage renal disease.
Neuropathy: Various nerve pathologies with symptoms determined by the nerves involved.
Such macrovascular problems are associated with atherosclerotic plaque formation, affecting blood supply to the heart, brain, limbs, and other organs. Later stages involve complete obstruction of these vessels, which can increase the risks of wider cardiovascular disease, including myocardial infarction, stroke, and gangrene (leading to amputation).
As in the previous section there is considerable evidence that a number of important plant constituents can improve endothelial integrity, and there are indications that this may reduce the incidence of diabetic complications.
Adipose-induced inflammation
Fatty tissues are inherently inflammatory. Adipose cells secrete a variety of cytokines, known as adipokines, including leptin, tumour necrosis factor (TNF)-α, and plasminogen-activator inhibitor type 1 (PAI-1). Fat tissue is also a key regulator of C-reactive protein.
Adipokines generate a state of low-grade generalised inflammation resulting in pathological defects in metabolism and blood flow. These inflammatory agents have been shown as a major mechanism for inducing insulin resistance and diabetes (2).
We shall see that there is promising research pointers to benefits of spices in reducing adipokine activities and in reducing the consequent rises in insulin resistance.
Management priority: Glycaemic control
It has long been confirmed that the most effective way to reduce diabetic complications is to bring down the raised levels of blood sugar that accompany the resistance to insulin.
The most useful first approach is to cut the rate at which glucose is produced and absorbed from food. This means at its simplest the reduction in amount of simple sugars, refined carbohydrates and alcohol in the diet and replacing them by complex, slow-release carbohydrates and proteins. To reduce complicating obesity and high cholesterol levels it also makes sense to cut back consumption of saturated fats.
A quick guide to the likelihood of a food pushing up blood glucose levels is its glycaemic index. This is defined by the American Diabetes Association as ‘a ranking of carbohydrates on a scale from 0 to 100 according to the extent to which they raise blood sugar levels after eating.’ Foods with a high GI are those which are rapidly digested and absorbed and result in marked fluctuations in blood sugar levels. Low-GI foods, by virtue of their slow digestion and absorption, produce gradual rises in blood sugar and insulin levels, and have proven benefits for health.
Low GI diets have been shown to improve both glucose and lipid levels in people with diabetes (type 1 and type 2). They have benefits for weight control because they help control appetite and delay hunger. Low GI diets also reduce insulin levels and insulin resistance.
A good GI Index is produced by the Harvard Medical School.
We shall see there are further ways in which we can reduce blood glucose levels using plant foods.
Fibre
There are several categories of fibre.
- β-glucans such as cellulose in cereals, fruit, vegetables (in all plants in general)
and the mushroom glucans
- Hemicelluloses in cereals, bran, legume
- Lignin invegetables, fruits and cereals
- Resistant starch in barley, wheat, legumes, bananas, etc.
- Fructans such as inulin in onions, bananas, leeks, Jerusalem artichokes, and asparagus
- Polyuronides such as pectin in the fruit skins and vegetables, and alginic acids in agar and other algae
Various fibres are known to have laxative effects, and assist with cholesterol lowering (3). Specific glucose management effects include
- attenuated blood glucose responses (4,5,6)
- prebiotic benefits on gut microbiome (increased Bifidobacteria, Lactobacilli, Faecalibacteria) (7)
- increased production of glucose-sparing short-chain fatty acids (SCFAs) (8)
- increased incretins: glucagon like peptide (GLP-1), peptide YY (PYY) (9)
- reduced body weight (10)
- reduced lipogenesis, adipogenesis, adipocyte numbers and size, inflammation, oxidative stress (11)
Apart form increasing the amount of wholegrains, vegetables, pulses and fruit in the diet, high fibre remedies include linseed (flaxseed), psyllium seed and husk, ispaghula, guar gum, and agar agar.
Bitters
Bitters have been used for their immediate effect in reducing sugar cravings associated with hypoglycaemic episodes. They have also been components of traditional formulations in diabetes, accompanied by hyperglycaemia. It has even been possible to speculate from these experiences that such an ‘adaptogenic’ effect is linked with a capacity to modulate insulin release.
Bitter principles in plants activate a family of around 30 receptors (TAS2Rs) tuned to each detect multiple bitter substances (perhaps as a defence mechanism against poisons) and with a wide range of physiological consequences, including changes in digestive activity (12,13) and an increase in blood flow to the digestive tract (14). They are found throughout the GI tract, airways, and other tissues (15), including pancreatic beta-cells. This latter location adds to the speculation that there is an explanation for the insulin modulating capacity of bitters.
Bitters have been shown to help manage glucose levels (16,17) with effects including the regulation of the hunger hormone ghrelin (18,19) increase in cholecystokinin (20) and regulation of key agents PYY and GLP-1 (21).
Classic bitter remedies associated with managing blood sugar levels include andrographis, neem, gentian root, wormwood, barberry bark (22) and golden seal.
Polyphenols
There is increasing evidence that polyphenols, including flavonoids, anthocyanidins (the colours of fruits and vegetables), have a significant effect in glycaemic control (23), and on various aspects of metabolic syndrome (24,25).
In one trial daily cranberry juice (240 mL) consumption for 12 weeks and blueberry extract or powder supplementation (= 9-10 mg of anthocyanins) for 8 to 12 weeks showed a beneficial effect on glucose control in late-onset diabetic subjects (26).
In a major study (PREDIMED-Plus) involving observations over several years of 7447 elderly participants at high cardiovascular risk, polyphenol intakes were calculated from food frequency questionnaires. Analyses were stratified by sex and BMI groups (overweight and obese). Consumption of polyphenols were inversely associated with incidence of type 2 diabetes, especially on women and those overweight (27). In a subgroup of 3430 elderly persons at higher cardiovascular risk in this same study, a high intake of total polyphenols was also associated with a reduced risk of diabetes (28).
There are several possible mechanisms for such benefits (29). A number of clinical trials point to an improvement of endothelial function in patients whose diets were supplemented with cocoa (30), green tea (31) and anthocyanin-rich berries (32,33,34).
Polyphenols are also prebiotic (35,36) and it may be that changes in gut microbiome can be a significant factor (37,38). The microbiota also process polyphenols (by cleavage into simple phenols) so that large molecules that are poorly absorbed become active modulators of inflammation (39).
Foods that are likely to be helpful in providing useful levels of polyphenols include berries, green tea and high-cocoa, low-sugar chocolate (which has been shown significantly to improve insulin sensitivity and lipid profile (40)), as well as a range of herbal products (41).
Spices
Common kitchen spices are showing increasing signs of being very important in the management of metabolic syndrome, blood sugar levels, and particularly vascular complications (42,43).
Cinnamon has been shown to directly regulate blood sugar levels (44,45), to reduce insulin resistance (46,47).
A beneficial effect of various spices on endothelial factors in diabetes is very likely (48).
Turmeric has been shown directly to interact with adipocytes to suppress adipokines. These curcumin-induced alterations reverse insulin resistance, hyperglycaemia, hyperlipidaemia, and other symptoms linked to obesity. Other structurally similar constituents derived from red chili, cinnamon, cloves, black pepper, and ginger, also exhibit effects against obesity and insulin resistance (49).
Turmeric, ginger and other spices also reduce inflammatory activity originating from adipose tissue (50,51)
Ginger has been shown to regulate blood sugar levels by increasing thermogenesis and lipolysis, suppressing lipogenesis, inhibiting intestinal fat absorption, and controlling appetite (52), as well as by reducing insulin resistance (53,54).
The Asian paradox
The rampant increase in the incidence of diabetes in India (55) and China suggests that a high daily spice intake is not sufficient protection against the condition. However the prevalence of peripheral vascular disease in these countries is lower than that reported in European populations (56,57). Levels of retinopathy approximately half that found in the west have been seen in India, Pakistan, Sri Lanka, China (58). This reduces the likelihood that this is due to genetic differences and reinforces the idea that there are dietary reasons, and that it is increased spice intake that reduces vascular complications of diabetes.
Herbal advice for diabetics
After basic exercise and low GI diet:
- Increase consumption in the diet of spices, especially cinnamon, turmeric and ginger.
- Increase polyphenol consumption: green tea, black currant, blueberry, pomegranate, with rewards of 70% chocolate, with any alcohol ration restricted to red wine!
- Ensure high fibre consumption, with supplementation by seaweed and seed sources.
- Consider supplements with spice extracts such as turmeric, and ginger (especially if extra heating appropriate) and also careful use of bitters.
All these measures are on the assumption that the diabetes is being managed without the use of insulin or other medical prescriptions. In these cases there needs to be more care, especially if glycaemic management is not stabilised, as too abrupt a change in regime might precipitate a glycaemic crisis. For the same reason it is not advisable to attempt to add to the management of Type 1 diabetes without careful coordination with medical professionals and monitoring of blood sugar levels.
References
- Mainous AG, Tanner RJ, Baker R, et al (2014) Prevalence of prediabetes in England from 2003 to 2011: population-based, cross-sectional study. BMJ Open 2014; 4: e005002.
- Kwon H, Pessin JE. (2013) Adipokines mediate inflammation and insulin resistance. Front Endocrinol. 12 (4): 71.
- Liu F, Prabhakar M, Ju J, et al. (2017) Effect of inulin-type fructans on blood lipid profile and glucose level: a systematic review and meta-analysis of randomized controlled trials. Eur J Clin Nutr. 71(1): 9-20.
- Silva FM, Kramer CK, de Almeida JC, et al. (2013) Fiber intake and glycemic control in patients with type 2 diabetes mellitus: a systematic review with meta-analysis of randomized controlled trials. Nutr Rev. 71(12): 790-801.
- Al-Mana NM, Robertson MD. (2018) Acute Effect of Resistant Starch on Food Intake, Appetite and Satiety in Overweight/Obese Males. Nutrients. 15;10 (12): 1993.
- Lin Y, Huybrechts I, Vereecken C, et al. (2015) Dietary fiber intake and its association with indicators of adiposity and serum biomarkers in European adolescents: the HELENA study. Eur J Nutr. 54(5): 771-82.
- Holscher HD. (2017) Dietary fiber and prebiotics and the gastrointestinal microbiota. Gut Microbes. 8(2): 172-184.
- van der Beek CM, Canfora EE, Kip AM, et al. (2018) The prebiotic inulin improves substrate metabolism and promotes short-chain fatty acid production in overweight to obese men. Metabolism. 87: 25-35.
- Klosterbuer AS, Thomas W, Slavin JL. (2012) Resistant starch and pullulan reduce postprandial glucose, insulin, and GLP-1, but have no effect on satiety in healthy humans. J Agric Food Chem. 60(48): 11928-34.
- Clark MJ, Slavin JL. (2013) The effect of fiber on satiety and food intake: a systematic review. J Am Coll Nutr. 32(3): 200-11.
- Rizkalla SW, Prifti E, Cotillard A, et al. (2012) Differential effects of macronutrient content in 2 energy-restricted diets on cardiovascular risk factors and adipose tissue cell size in moderately obese individuals: a randomized controlled trial. Am J Clin Nutr. 95(1):49-63.
- Sternini C. (2007) Taste receptors in the gastrointestinal tract. IV. Functional implications of bitter taste receptors in gastrointestinal chemosensing. Am J Physiol Gastrointest Liver Physiol. 292 (2): G457-61.
- Posovszky C, Wabitsch M. (2015) Regulation of appetite, satiation, and body weight by enteroendocrine cells. Part 1: characteristics of enteroendocrine cells and their capability of weight regulation. Horm Res Paediatr. 83(1): 1-10.
- McMullen MK, Whitehouse JM, Towell A. (2015) Bitters: Time for a New Paradigm. Evid Based Complement Alternat Med. 2015: 670504.
- Behrens M, Meyerhof W. (2006) Bitter taste receptors and human bitter taste perception. Cell Mol Life Sci. 63(13): 1501-9.
- Palatini, K., Wilson, M., Alley, J., et al. (2015), Diverse Classes of Bitter Phytochemicals Modulate Carbohydrate Metabolism and Immune Responses through Gastrointestinal Bitter Taste Receptors. The FASEB Journal, 29: 405-5.
- Dotson CD, Zhang L, Xu H, et al. (2008) Bitter taste receptors influence glucose homeostasis. PLoS One. 3(12): e3974.
- Janssen S, Laermans J, Verhulst PJ, et al. (2011) Bitter taste receptors and α-gustducin regulate the secretion of ghrelin with functional effects on food intake and gastric emptying. Proc Natl Acad Sci U S A. 108(5): 2094-9.
- Calvo SS, Egan JM. (2015) The endocrinology of taste receptors. Nat Rev Endocrinol. 11(4): 213-27.
- Jeon T-I, Seo Y-K, and Osborne TF (2011) Gut Bitter Taste Receptor Signaling Induces ABCB1 through a Mechanism Involving CCK. Biochem J. 15; 438(1): 33–37.
- Posovszky, C, and Wabitsch M. (2015) Regulation of appetite, satiation, and body weight by enteroendocrine cells. Part 1: characteristics of enteroendocrine cells and their capability of weight regulation. Hormone Research in Paediatrics 83.1: 1-10.
- Zhao Y, Yang YY, Yang BL, et al. (2021) Efficacy and safety of berberine for dyslipidemia: study protocol for a randomized double-blind placebo-controlled trial. Trials. 22(1): 85.
- Rienks J, Barbaresko J, Oluwagbemigun K, et al. (2018) Polyphenol exposure and risk of type 2 diabetes: dose-response meta-analyses and systematic review of prospective cohort studies. Am J Clin Nutr. 108(1): 49-61.
- Amiot MJ, Riva C, Vinet A. (2016) Effects of dietary polyphenols on metabolic syndrome features in humans: a systematic review. Obes Rev. 17(7): 573-86.
- Raman G, Avendano EE, Chen S, et al. (2019) Dietary intakes of flavan-3-ols and cardiometabolic health: systematic review and meta-analysis of randomized trials and prospective cohort studies. Am J Clin Nutr. 110(5): 1067-1078.
- Rocha DMUP, Caldas APS, da Silva BP et al. (2019) Effects of blueberry and cranberry consumption on type 2 diabetes glycemic control: A systematic review. Crit Rev Food Sci Nutr. 59(11): 1816-1828.
- Tresserra-Rimbau A, Castro-Barquero S, Vitelli-Storelli F, et al. (2019) Associations between Dietary Polyphenols and Type 2 Diabetes in a Cross-Sectional Analysis of the PREDIMED-Plus Trial: Role of Body Mass Index and Sex. Antioxidants (Basel). 8(11): 537.
- PREDIMED study investigators. (2015) Intake of Total Polyphenols and Some Classes of Polyphenols Is Inversely Associated with Diabetes in Elderly People at High Cardiovascular Disease Risk. J Nutr. 146(4): 767-777.
- Munir KM, Chandrasekaran S, Gao F, Quon MJ. (2013) Mechanisms for food polyphenols to ameliorate insulin resistance and endothelial dysfunction: therapeutic implications for diabetes and its cardiovascular complications. Am J Physiol Endocrinol Metab. 305(6): E679-86.
- Sun Y , Zimmermann D , De Castro CA , Actis-Goretta L . (2019) Dose-response relationship between cocoa flavanols and human endothelial function: a systematic review and meta-analysis of randomized trials. Food Funct. 10(10): 6322-6330.
- Alexopoulos N, Vlachopoulos C, Aznaouridis K, et al. (2008) The acute effect of green tea consumption on endothelial function in healthy individuals. Eur J Cardiovasc Prev Rehabil. 15(3): 300-5.
- Amiot MJ, Riva C, Vinet A. (2016) Effects of dietary polyphenols on metabolic syndrome features in humans: a systematic review. Obes Rev. 17(7): 573-86.
- Martini D, Marino M, Angelino D, et al. (2020) Role of berries in vascular function: a systematic review of human intervention studies. Nutr Rev. 78(3): 189-206.
- Fairlie-Jones L, Davison K, Fromentin E, Hill AM. (2017) The Effect of Anthocyanin-Rich Foods or Extracts on Vascular Function in Adults: A Systematic Review and Meta-Analysis of Randomised Controlled Trials. Nutrients. 9(8): 908.
- Igwe EO, Charlton KE, Probst YC, et al. (2019) A systematic literature review of the effect of anthocyanins on gut microbiota populations. J Hum Nutr Diet. 32(1): 53-62.
- Bond T, Derbyshire E. (2019) Tea Compounds and the Gut Microbiome: Findings from Trials and Mechanistic Studies. Nutrients. 11(10): 2364.
- Ejtahed HS, Angoorani P, Soroush AR. (2020) Gut microbiota-derived metabolites in obesity: a systematic review. Biosci Microbiota Food Health. 39(3): 65-76.
- Houghton D, Hardy T, Stewart C, et al. (2018) Systematic review assessing the effectiveness of dietary intervention on gut microbiota in adults with type 2 diabetes. Diabetologia. 61(8): 1700-1711.
- Nash V, Ranadheera CS, Georgousopoulou EN, et al.(2018) The effects of grape and red wine polyphenols on gut microbiota – A systematic review. Food Res Int. 113: 277-287.
- Lin X, Zhang I, Li A, et al. (2016) Cocoa Flavanol Intake and Biomarkers for Cardiometabolic Health: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Nutr. 146(11): 2325-2333.
- Ejtahed HS, Soroush AR, Siadat SD, et al. (2019) Targeting obesity management through gut microbiota modulation by herbal products: A systematic review. Complement Ther Med. 42: 184-204.
- Panickar KS. (2013) Beneficial effects of herbs, spices, and medicinal plants on the metabolic syndrome, brain, and cognitive function. Cent Nerv Syst Agents Med Chem. 13(1): 13-29.
- Skulas-Ray AC, Kris-Etherton PM, Teeter DL, et al. (2011) A high antioxidant spice blend attenuates postprandial insulin and triglyceride responses and increases some plasma measures of antioxidant activity in healthy, overweight men. J Nutr. 141(8): 1451-7.
- Namazi N, Khodamoradi K, Khamechi SP, et al. (2019) The impact of cinnamon on anthropometric indices and glycemic status in patients with type 2 diabetes: A systematic review and meta-analysis of clinical trials. Complement Ther Med. 43: 92-101
- Deyno S, Eneyew K, Seyfe S, et al. (2019) Efficacy and safety of cinnamon in type 2 diabetes mellitus and pre-diabetes patients: A meta-analysis and meta-regression. Diabetes Res Clin Pract. 156:107815
- Sheng X, Zhang Y, Gong Z, et al. (2008) Improved Insulin Resistance and Lipid Metabolism by Cinnamon Extract through Activation of Peroxisome Proliferator-Activated Receptors. PPAR Res. 2008:581348.
- Qin B, Panickar KS, Anderson RA. (2010) Cinnamon: potential role in the prevention of insulin resistance, metabolic syndrome, and type 2 diabetes. J Diabetes Sci Technol. 4(3): 685-93.
- Azimi P, Ghiasvand R, Feizi A, et al. (2016 Effect of cinnamon, cardamom, saffron and ginger consumption on blood pressure and a marker of endothelial function in patients with type 2 diabetes mellitus: A randomized controlled clinical trial. Blood Press. 25(3):133-40.
- Aggarwal BB. (2010) Targeting inflammation-induced obesity and metabolic diseases by curcumin and other nutraceuticals. Annu Rev Nutr. 30:173-99.
- Woo HM, Kang JH, Kawada T, et al. (2007) Active spice-derived components can inhibit inflammatory responses of adipose tissue in obesity by suppressing inflammatory actions of macrophages and release of monocyte chemoattractant protein-1 from adipocytes. Life Sci. 80(10): 926-31
- Ebrahimzadeh Attari V, Ostadrahimi A, Asghari Jafarabadi M, et al. (2016) Changes of serum adipocytokines and body weight following Zingiber officinale supplementation in obese women: a RCT. Eur J Nutr. 55(6): 2129-36
- Ebrahimzadeh Attari V, Malek Mahdavi A, Javadivala Z, et al. (2018) A systematic review of the anti-obesity and weight lowering effect of ginger (Zingiber officinale Roscoe) and its mechanisms of action. Phytother Res. 32(4): 577-585
- Li Y, Tran VH, Kota BP, et al. (2014) Preventative Effect of Zingiber Officinale on Insulin Resistance and its Mechanism of Action. Basic Clin Pharmacol Toxicol. 115 (2): 209-215.
- Mahluji S, Attari VE, Mobasseri M, et al.(2013) Effects of ginger (Zingiber officinale) on plasma glucose level, HbA1c and insulin sensitivity in type 2 diabetic patients. Int J Food Sci Nutr. 64(6): 682-6.
- Ramachandran A, Snehalatha C. (2009) Current scenario of diabetes in India. J Diabetes. 1(1): 18-28.
- Premalatha G, Shanthirani S, Deepa R, et al.(2000) Prevalence and risk factors of peripheral vascular disease in a selected south Indian population. Diabetes Care. 23: 1295–300.
- Ramachandran A, Snehalatha C, Satyavani K et al. (1999) Prevalence of vascular complications and their risk factors in type 2 diabetes. J Assoc Physicians India. 47: 1152–6.
- Narendran V, John R K, Raghuram A. (2002) Diabetic retinopathy among self reported diabetics in southern India: a population based assessment. Br J Ophthalmol 86(9): 1014–1018
