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).
The drug reduces the amount of glucose made by the liver, and is frequently prescribed because it has been found to help prevent many of the long-term complications of diabetes. Metformin is usually taken without another drug, usually at a dose of 500 milligrams (mg) a day, depending on the brand, to start. Doses are not to exceed 2,000 or 2,500 mg per day.
Together with evidence of normalization of insulin secretion after bariatric surgery (84), insights into the behavior of the liver and pancreas during hypocaloric dieting lead to a hypothesis of the etiology and pathogenesis of type 2 diabetes (Fig. 6): The accumulation of fat in liver and secondarily in the pancreas will lead to self-reinforcing cycles that interact to bring about type 2 diabetes. Fatty liver leads to impaired fasting glucose metabolism and increases export of VLDL triacylglycerol (85), which increases fat delivery to all tissues, including the islets. The liver and pancreas cycles drive onward after diagnosis with steadily decreasing β-cell function. However, of note, observations of the reversal of type 2 diabetes confirm that if the primary influence of positive calorie balance is removed, then the processes are reversible (21).
I bring this up because sleep apnea increases a person’s risk for developing type 2 diabetes. Also, sleep-disordered breathing is also related to proper nutrition throughout life. And perhaps most importantly, the first line of defense in catching sleep-disordered breathing in patients early, are dentists. This is another area where dentists must get involved if we want to tackle the issue of pervasive type 2 diabetes with any success.
Diabetes is a disease characterized by a person’s inability to process carbohydrates, a condition that if untreated can lead to often-catastrophic health consequences: lethargy, diminished eyesight, heart attacks, strokes, blindness and a loss of circulation in the feet that could lead to amputation. The Centers for Disease Control and Prevention estimate that in 2014, about 29 million Americans – almost 1 in 10 – had diabetes.
This seems hard to do, but really it’s not if you know one secret: Replace snacking with something far more satisfying — fat. That’s right, the government is wrong to recommend a low fat diet. Fat is what makes you feel full until your next meal. Take away the fat, take away the full. Don’t go to an extreme, but do lean strongly toward a high-fat low-carb diet.