Within the hepatocyte, fatty acids can only be derived from de novo lipogenesis, uptake of nonesterified fatty acid and LDL, or lipolysis of intracellular triacylglycerol. The fatty acid pool may be oxidized for energy or may be combined with glycerol to form mono-, di-, and then triacylglycerols. It is possible that a lower ability to oxidize fat within the hepatocyte could be one of several susceptibility factors for the accumulation of liver fat (45). Excess diacylglycerol has a profound effect on activating protein kinase C epsilon type (PKCε), which inhibits the signaling pathway from the insulin receptor to insulin receptor substrate 1 (IRS-1), the first postreceptor step in intracellular insulin action (46). Thus, under circumstances of chronic energy excess, a raised level of intracellular diacylglycerol specifically prevents normal insulin action, and hepatic glucose production fails to be controlled (Fig. 4). High-fat feeding of rodents brings about raised levels of diacylglycerol, PKCε activation, and insulin resistance. However, if fatty acids are preferentially oxidized rather than esterified to diacylglycerol, then PKCε activation is prevented, and hepatic insulin sensitivity is maintained. The molecular specificity of this mechanism has been confirmed by use of antisense oligonucleotide to PKCε, which prevents hepatic insulin resistance despite raised diacylglycerol levels during high-fat feeding (47). In obese humans, intrahepatic diacylglycerol concentration has been shown to correlate with hepatic insulin sensitivity (48,49). Additionally, the presence of excess fatty acids promotes ceramide synthesis by esterification with sphingosine. Ceramides cause sequestration of Akt2 and activation of gluconeogenic enzymes (Fig. 4), although no relationship with in vivo insulin resistance could be demonstrated in humans (49). However, the described intracellular regulatory roles of diacylglycerol and ceramide are consistent with the in vivo observations of hepatic steatosis and control of hepatic glucose production (20,21).
Greek clover is an annual herb with aromatic seeds having medicinal properties. It is also known as fenugreek, and is largely used in curry. Greek clover has properties to lower down the levels of glucose in the body, which, in turn, controls diabetes. Also, when given in changeable doses of 25 gm to 100 gm on a daily basis, it was found to diminish reactive hyperglycemia in diabetic patients. Furthermore, levels of glucose, serum cholesterol, and triglycerides were also appreciably reduced. Alternatively, one can just stir two teaspoons of Greek clover seeds in powder form in warm milk and consume on a regular basis; it will control the levels of blood sugar and keep diabetes at bay. In case one does not want to have the powder in milk, seeds can be eaten wholly, too.
The diagnosis of diabetes, and the effectiveness of treatments can be objectively measured. Fasting plasma glucose (FPG) measurements and then the oral glucose tolerance test accurately measure insulin function, and guide diagnosis. While routine blood sugar monitoring (with test strips) is generally unnecessary in Type 2 diabetes, measurement gives a point estimate of blood sugar levels. Glyclated hemoglobin (A1C) levels reflect overall blood sugar trends, with higher levels associated with more complications of the disease. Interestingly, super-intensive blood glucose lowering isn’t associated with additional risk reduction, and it increases the risk of side effects due to too-low blood sugar. Treatment goals are individualized (hey, it’s “holistic”), balancing a number of factors including risks as well as a patient’s ability to manage complex treatment plans.
Magnesium is high in green leafy vegetables, nuts, beans, and grains, but we remove most beans and all grains from the diet of patients, which is why using magnesium as part of a natural remedy for diabetes can be beneficial. Low intracellular magnesium can cause insulin resistance. Dosing of up to 500 mg a day is fine, but higher than that may result in diarrhea in patients.
Insulin is a hormone that helps glucose get where it needs to go. When your body senses that you’ve eaten something, your pancreas produces insulin to help your cells absorb sugar. If you didn’t have insulin, your cells wouldn’t receive their glucose fuel, and your body would sense sugar in your bloodstream and eventually store it as fat because your cells didn’t use it.
The bottom line is that diabetes can be bad news—but this doesn’t have to be the case. Interventions can prevent or delay the disease in people with prediabetes. The Diabetes Prevention Program (DPP), a large study of people at high risk of diabetes, has established a prevention plan that’s both feasible and cost-effective. The DPP showed that weight loss and increased physical activity reduced the development of type 2 diabetes by 58% during a three-year period.
Melissa Conrad Stöppler, MD, is a U.S. board-certified Anatomic Pathologist with subspecialty training in the fields of Experimental and Molecular Pathology. Dr. Stöppler's educational background includes a BA with Highest Distinction from the University of Virginia and an MD from the University of North Carolina. She completed residency training in Anatomic Pathology at Georgetown University followed by subspecialty fellowship training in molecular diagnostics and experimental pathology.