^ Jump up to: a b Cox DJ, Kovatchev BP, Anderson SM, Clarke WL, Gonder-Frederick LA (November 2010). "Type 1 diabetic drivers with and without a history of recurrent hypoglycemia-related driving mishaps: physiological and performance differences during euglycemia and the induction of hypoglycemia". Diabetes Care. 33 (11): 2430–35. doi:10.2337/dc09-2130. PMC 2963507. PMID 20699432.
Type 2 diabetes has long been known to progress despite glucose-lowering treatment, with 50% of individuals requiring insulin therapy within 10 years (1). This seemingly inexorable deterioration in control has been interpreted to mean that the condition is treatable but not curable. Clinical guidelines recognize this deterioration with algorithms of sequential addition of therapies. Insulin resistance and β-cell dysfunction are known to be the major pathophysiologic factors driving type 2 diabetes; however, these factors come into play with very different time courses. Insulin resistance in muscle is the earliest detectable abnormality of type 2 diabetes (2). In contrast, changes in insulin secretion determine both the onset of hyperglycemia and the progression toward insulin therapy (3,4). The etiology of each of these two major factors appears to be distinct. Insulin resistance may be caused by an insulin signaling defect (5), glucose transporter defect (6), or lipotoxicity (7), and β-cell dysfunction is postulated to be caused by amyloid deposition in the islets (8), oxidative stress (9), excess fatty acid (10), or lack of incretin effect (11). The demonstration of reversibility of type 2 diabetes offers the opportunity to evaluate the time sequence of pathophysiologic events during return to normal glucose metabolism and, hence, to unraveling the etiology.
In the twentieth century, insulin was available only in an injectable form that required carrying syringes, needles, vials of insulin, and alcohol swabs. Clearly, patients found it difficult to take multiple shots each day; as a result, good blood sugar control was often difficult. Many pharmaceutical companies now offer discreet and convenient methods for delivering insulin.
Although a close relationship exists among raised liver fat levels, insulin resistance, and raised liver enzyme levels (52), high levels of liver fat are not inevitably associated with hepatic insulin resistance. This is analogous to the discordance observed in the muscle of trained athletes in whom raised intramyocellular triacylglycerol is associated with high insulin sensitivity (53). This relationship is also seen in muscle of mice overexpressing the enzyme DGAT-1, which rapidly esterifies diacylglycerol to metabolically inert triacylglycerol (54). In both circumstances, raised intracellular triacylglycerol stores coexist with normal insulin sensitivity. When a variant of PNPLA3 was described as determining increased hepatic fat levels, it appeared that a major factor underlying nonalcoholic fatty liver disease and insulin resistance was identified (55). However, this relatively rare genetic variant is not associated with hepatic insulin resistance (56). Because the responsible G allele of PNPLA3 is believed to code for a lipase that is ineffective in triacylglycerol hydrolysis, it appears that diacylglycerol and fatty acids are sequestered as inert triacylglycerol, preventing any inhibitory effect on insulin signaling.
Effect of an 8-week very-low-calorie diet in type 2 diabetes on arginine-induced maximal insulin secretion (A), first phase insulin response to a 2.8 mmol/L increase in plasma glucose (B), and pancreas triacylglycerol (TG) content (C). For comparison, data for a matched nondiabetic control group are shown as ○. Replotted with permission from Lim et al. (21).
8. Get your protein from vegetable sources, fish, and dairy: Plant-based proteins have a balanced nutritional profile (providing fiber, fat, and protein) and are low in saturated fats. Some saturated fats, like those that are heavily processed or from unhealthy animals, can be dangerous, as they raise cholesterol levels and contribute to heart disease. Dairy from pastured animals (such as yogurt) that is low in sugar provides protein, carbohydrates, and beneficial probiotics, and non-mercury contaminated, wild caught fish is a great source of protein that is low in saturated fat and high in amino acids and fatty acids like Omega-3.
The twin cycle hypothesis of the etiology of type 2 diabetes. During long-term intake of more calories than are expended each day, any excess carbohydrate must undergo de novo lipogenesis, which particularly promotes fat accumulation in the liver. Because insulin stimulates de novo lipogenesis, individuals with a degree of insulin resistance (determined by family or lifestyle factors) will accumulate liver fat more readily than others because of higher plasma insulin levels. In turn, the increased liver fat will cause relative resistance to insulin suppression of hepatic glucose production. Over many years, a modest increase in fasting plasma glucose level will stimulate increased basal insulin secretion rates to maintain euglycemia. The consequent hyperinsulinemia will further increase the conversion of excess calories to liver fat. A cycle of hyperinsulinemia and blunted suppression of hepatic glucose production becomes established. Fatty liver leads to increased export of VLDL triacylglycerol (85), which will increase fat delivery to all tissues, including the islets. This process is further stimulated by elevated plasma glucose levels (85). Excess fatty acid availability in the pancreatic islet would be expected to impair the acute insulin secretion in response to ingested food, and at a certain level of fatty acid exposure, postprandial hyperglycemia will supervene. The hyperglycemia will further increase insulin secretion rates, with consequent enhancement of hepatic lipogenesis, spinning the liver cycle faster and driving the pancreas cycle. Eventually, the fatty acid and glucose inhibitory effects on the islets reach a trigger level that leads to a relatively sudden onset of clinical diabetes. Figure adapted with permission from Taylor (98).
Cinnamon’s effectiveness as a treatment for diabetes has not been established. A prescription drug as ineffective as cinnamon likely wouldn’t pass FDA muster. Existing drug treatments for diabetes, on the other hand, are cheap, effective, and generally well tolerated. Compared to drug therapy, we don’t know if cinnamon can reduce the risk of mortality due to diabetes, or the progression to any of the other serious outcomes of diabetes. For my patients that insist on trying cinnamon, I’d caution them of the risks, and reinforce that cinnamon is no alternative for lifestyle changes and medication if necessary. It may be natural, sure, but that doesn’t mean it’s either safe or effective.
According to studies, cinnamon may have a positive effect on the glycemic control and the lipid profile in patients with diabetes mellitus type 2. This is because it contains 18% polyphenol content in dry weight. This popular Indian spice can improve insulin sensitivity and blood glucose control. According to a study published in Journal Of The American Board Of Family Medicine, “cinnamon lowered HbA1C by 0.83% compared with standard medication alone lowering HbA1C 0.37%. Taking cinnamon could be useful for lowering serum HbA1C in type 2 diabetics with HbA1C >7.0 in addition to usual care.”
Exenatide (Byetta) was the first drug of the GLP-1 agonist group. It originated from an interesting source, the saliva of the Gila monster. Scientists observed that this small lizard could go a long time without eating. They discovered a substance in its saliva that slowed stomach emptying, thus making the lizard feel fuller for a longer time. This substance resembled the hormone GLP-1.