Question

A patient has been diagnosed with type II diabetes. Discuss the differences in terms of dietary and pharmacologic management between type I and type II diabetes.

Answer 1

In Type 1 diabetes the pancreas can do longer release insulin. The high blood sugar that results can lead to complications such as kidney, nerve, and eye damage, and cardiovascular disease. Glycemic index and glycemic load are scientific terms used to measure he impact of a food on blood sugar. Foods with low glycemic load raise blood sugar modestly, and thus are better choices for people with diabetes. Meal timing is very important for people with type 1 diabetes. Meals must match insulin doses. Eating meals with a low glycemic load makes meal timing easier. Low glycemic load meals raise blood sugar slowly and steadily, leaving plenty of time for the body (or the injected insulin dose) to respond. Skipping a meal or eating late puts a person at risk for low blood sugar(hypoglycemia). Foods to eat for a type 1 diabetic diet include complex carbohydrates such as brown rice,whole wheat,quinoa,oatmeal,fruits,vegetables,beans, and lentils. Foods to avoid for a type 1 diabetes diet include sodas (both diet and regular),simple carbohydrates processed/refined sugars (white bread, pastries, chips, cookies, pastas),trans fats (anything with the word hydrogenated on the label), and high-fat animal products. Fats don't have much of a direct effect on blood sugar but they can be useful in slowing the absorption of carbohydrates. Protein provides steady energy with little effect on blood sugar. It keeps blood sugar stable, and can help with sugar cravings and feeling full after eating. Protein-packed foods to include on your menu are beans, legumes, eggs, seafood, dairy, peas, tofu, and lean meats and poultry.Five type 1 diabetes"superfoods" to eat include fiber, sardines, vinegar, cinnamon, and berries.The Mediterranean dietplan is often recommended for people with type 1 diabetes because it is full of nutrient-dense foods, including lots of fresh vegetables, some fruit, plant-fats such as olive oil and nuts, fish such as sardines, and occasional meat and dairy. While there are no absolute diet restrictions in type 1 diabetes, healthier food choices can make control a lot easier. For example, meal timing is very important for people with type 1 diabetes. Meals must match insulin doses.
Most people with type 1 diabetes use a long-acting insulin (also called basal insulin or NPH), which means it will continue to lower blood sugar over 24 hours. This means it will lower blood sugar even if there is no glucose from dietary carbohydrates to act upon. Because of this, skipping a meal or eating late puts a person at risk for low blood sugar (hypoglycemia).

On the other hand, eating a larger meal or a meal that contains more carbohydrates that normal will raise blood sugar more than the basal insulin can dispose of. In this situation, a short-acting insulin (also called regular insulin) must be given in the appropriate dose to match the carbohydrate content of the meal and the level of blood glucose before eating. Eating meals with a low glycemic load (index) makes meal timing easier. Low glycemic load meals raise blood sugar slowly and steadily, leaving plenty of time for the body (or the injected insulin dose) to respond.

People who use continuous glucose monitoring and insulin pumps instead of finger sticks and injecting insulin have a little more flexibility in their meal timing because they have real-time feedback to help them match carbohydrate intake with insulin. However, everyone benefits from becoming more aware of their dietary intake, making diet restrictions to stay consistent with a low glycemic load diet, and matching their meals with appropriate insulin doses.

Paying attention to meal timing and glycemic load enables people with type 1 diabetes to keep their blood glucose levels relatively stable. Stable blood sugar prevents the complications of hypoglycemia and hyperglycemia1. Recent studies have provided contradictory data regarding the benefit of better glycemic control in preventing cardiovascular disease. While we used to think hyperglycemia was worse, the data show increased risk of cardiovascular disease when hypoglycemia is common2. Research tells us that maintaining an overall stable blood sugar (few highs or lows) is best for preventing complications of any kind. Low glycemic load eating and consistent meal timing are the best ways to achieve this. While some people go overboard with diet restriction, it is also important to consider the nutritional balance (fat, protein, and carbohydrates) in a meal. Specifically, fat, protein, and fiber all slow down the absorption of carbohydrates, and thus allow time for insulin to work, gradually moving glucose out of the blood and into the target tissues. Slower digestion and absorption maintains a more stable blood sugar level.
Metformin is the most widely used drug, together with sodium glucose co-transporters 2 (SGLT2) inhibitors, amylin analogues, glucagon-like peptide 1 (GLP-1) receptor agonists, and dipeptidyl peptidase-4 (DPP-4) inhibitors. Many people with type 1 diabetes live long, healthy lives. The key to good health is keeping your blood sugar levels within your target range, which can be done with meal planning, exercise and intensive insulin therapy. All people with type 1 diabetes must use insulin injections to control their blood glucose. The basis of treatment in autoimmune diabetes is insulin therapy; however, many clinical cases have proven that this method does not solve all problems. Trials of causal treatment including blocking the autoimmune processes and insulin producing cells transplants were carried out. Those methods require more research to be concerned as efficient and safe ways of treatment in type 1 diabetes. The use of non-insulin adjunct treatment is a new trend. It has been successfully used in laboratories as well as clinical trials. Metformin is the most widely used drug, together with sodium glucose co-transporters 2 (SGLT2) inhibitors, amylin analogues, glucagon-like peptide 1 (GLP-1) receptor agonists, and dipeptidyl peptidase-4 (DPP-4) inhibitors. The results of administration of these medicaments give good outcomes in patients with diabetes mellitus type 1. Most likely, in the near future, they will progressively be used in both adult and adolescent patients with type 1 diabetes. Further multicenter, randomized studies are required to evaluate the efficacy of treatment and long term safety of these drugs. Whereas, dietary management of type 2 diabetes are Diets rich in whole grains, fruits, vegetables, legumes, nuts, moderate in alcohol consumption, and lower in refined grains, red/processed meats, and sugar sweetened beverages have demonstrated to reduce diabetes risk and improve glycemic control and blood lipids in patients with diabetes. Sugar sweetened beverages. Sugary beverages are the worst drink choice for someone with diabetes.Trans fats. Artificial trans fats are extremely unhealthy.White bread, rice, and pasta.Fruit-flavored yogurt.Sweetened breakfast cereals.Flavored coffee drinks.Honey, agave nectar, and maple syrup.Dried fruit.Pharmacological management of type 2 diabetes are :
Metformin is unequivocally the first line treatment in patients with type 2 diabetes. It belongs to the biguanide class of drugs and acts by increasing hepatic insulin sensitivity. It also increases the uptake of glucose into peripheral cells, reduces hepatic glucose production and aids weight loss. Metformin can induce gastrointestinal side effects such as abdominal bloating, cramps, nausea, vomiting and diarrhoea, which can be mitigated by starting metformin at a low dose.The British National Formulary recommends starting at 500mg of metformin once daily for at least a week prior to titrating the dose up to a maximum to 2g daily in divided doses. Caution is advised when used in patients with impaired renal function or other conditions that may increase the risk of lactic acidosis, such as acute heart failure or shock. However, a Cochrane review of trials that included patients on metformin suggests that the potential risk of developing lactic acidosis is often overstated.
Sulfonylureas (e.g. gliclazide, glimepiride, meglitinides) are commonly used as second line agents in patients with type 2 diabetes, but can also be used as an alternative first line treatment instead of metformin if the patient is not overweight, or is unable to tolerate metformin. Sulfonylureas can also be added to metformin if glycaemic control is inadequate. Sulfonylureas act by binding to a specific receptor on pancreatic beta cells, leading to increased secretion of endogenous insulin. The main side effects of sulfonylureas are weight gain and hypoglycaemia, and risk is increased in people with mild to moderate renal impairment and severe hepatic impairment.

Thiazolidinediones (e.g. pioglitazone) are an alternative second line or a third line therapy, although they have increasingly lost favour because of their adverse effects. The National Institute for Health and Care Excellence (NICE) recommends that they should be considered as second line therapies, in addition to metformin, if the risk of hypoglycaemia with sulphylureas would be unacceptable, for example if a patient lives alone in vulnerable circumstances or if sulphonylureas are not tolerated. NICE suggests that in these cases the risks and benefits should be discussed with each patient. Thiazolidinediones act via the peroxisome proliferator-activated receptor, a nuclear transcription factor to decrease insulin resistance and have been shown to lead to a significant reduction in HbA1C, both as a monotherapy and when used in combination with other oral agents such as metformin and or sulphonylureas. Thiazolidinediones are associated with an increased fracture risk and in some patients may have led to heart failure. In 2010, the European Medicines Agency (EMA) suspended marketing authorisation for rosiglitazone as new evidence suggested that its cardiovascular risks outweighed its benefits. There is also a possible increased risk of bladder cancer with use of pioglitazone.

Insulin replacement therapy will eventually be required in the majority of patients with type 2 diabetes. Ideally, this would mimic the normal pattern of insulin secretion, where a background level of insulin is supplemented by higher release of insulin to match the glucose load following a meal. Oral agents are usually continued in patients who are starting insulin, but this may need to be reviewed if hypoglycaemia is a problem. Broadly, there are three strategies of insulin replacement; a basal insulin alone, twice daily biphasic insulin containing a mix of rapid acting and long acting insulins and a basal bolus regimen with a long acting insulin, with additional doses of a short acting insulin given at meal times. Patients with type 2 diabetes who are already taking oral agents may initially only need a long acting basal insulin to improve their glycaemic control. Alternatively, a twice daily premixed insulin can be used to provide both a long acting and short acting insulin. This is potentially more convenient, but is less flexible than other regimens and may be better for patients with regimented mealtimes. A basal bolus regimen is more flexible but has the disadvantage of requiring four injections each day. All insulin regimens are associated with an increased risk of hypoglycaemia and can cause weight gain. In addition, fear of injections, perceived complexity of the treatment regimens, and concern about failure to self manage the disease can form barriers to starting insulin treatment.

Newer therapies targeting the incretin axis
In recent years, greater understanding of the normal physiology of insulin release and technological advances in drugs and therapeutics has led to new targets to improve glycaemic control. One such target is the incretin axis. In non-diabetic individuals, the insulin response is increased following ingestion of food as a result of the release of incretin hormones including glucagon-like peptide-1 (GLP-1). This response is reduced in patients with diabetes. The incretin hormones lead to glucose dependent insulin release and reduced glucagon release. In vivo the incretin hormones are quickly broken down by the hormone dipeptidyl peptidase-4 (DDP4).

In vivo, endogenous GLP-1 has a half-life of a few minutes as it is rapidly degraded by DDP4. GLP-1 receptor agonists (e.g. exenatide, liraglutide, lixisenatide, dulaglutide) target the incretin axis by increasing the action of GLP-1. Exenatide is derived from the saliva of the Gila monster and is structurally similar to GLP-1, leading to longer lasting glucose dependent insulin release. Liraglutide is another synthetic GLP-1 which resists degradation by DDP4 by fatty acid substitution. Collectively, GLP-1 receptor agonists increase insulin release, decrease glucagon release and slow gastric emptying (see ‘Actions of newer diabetes therapies targeting the incretin axis’). In contrast to many diabetes treatments, GLP-1 receptor agonists aid weight loss, and liraglutide was recently licensed for non-diabetic individuals as a weight loss treatment. A common side effect of GLP-1 receptor agonists is nausea, which is usually temporary and disappears around two weeks after treatment initiation. In addition, GLP-1 receptors also increase satiety and augment weight loss. At present, GLP-1 receptor agonists are only available in an injectable form.

DDP4 inhibitors (e.g. sitagliptin, linagliptin, saxagliptin, vildagliptin) are recommended by NICE as an alternative second-line or third-line therapy. Because of their mechanism of action, DDP4 inhibitors have a low risk of hypoglycaemia and do not lead to weight gain.

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Newer therapies targeting renal glucose handling

Sodium glucose co transporter 2 (SGLT2) inhibitors (e.g. dapagliflozin, canagliflozin, empagliflozin) are more suitably termed as ‘gluco-uretic’ agents and provide a novel target for controlling blood sugar levels via the kidneys. Under normal conditions, glucose is filtered out of the blood by the kidneys via a transporter protein (SGLT-2). By blocking the action of these transporters, more glucose is excreted in the urine. SGLT2 inhibitors lower blood glucose with a low risk of hypoglycaemia. The increased excretion of glucose can cause osmotic effects that may lead to hypotension and dehydration, particularly in patients taking diuretics. They also result in modest improvements in weight and blood pressure. The main side effects of SGLT2 inhibitors are an increase in fungal genital infections and urinary tract infections; an effect seen more commonly in women then in men.

Newer insulins
Longer acting insulins have been developed to provide a more stable basal insulin profile over a 24-hour period. The action of insulin can be delayed by increasing its molecular size and slowing its absorption. Degludec is formed of hexameric chains that slowly separate, releasing the active monomer that can then be absorbed. In clinical trials, in patients with type 2 diabetes, it was non inferior to glargine and had lower levels of hypoglycaemic episodes, particularly at night (nocturnal hypoglycaemia). The long half-life of degludec compared with traditional, long-acting insulins means that patients can be much more flexible about the timing of their basal insulin doses, without compromising their glycaemic control. This may be particularly useful for people with erratic lifestyles. Glargine U300 (Toujeo) is a more concentrated form of insulin glargine available as 300 units/ml in a pre-filled pen. U300 also has a longer half-life compared with glargine. In trials, it was associated with fewer nocturnal hypoglycaemic episodes than glargine, with no change in the overall glycaemic control.The need to regularly inject insulin can be a barrier for optimal treatment for many patients. Novel delivery routes, such as inhaled insulin, may lead to better compliance and control. Inhaled insulin, now available in many countries as Afrezza, utilises the large and well perfused surface area of the lungs for uptake of microparticles containing short acting insulin[24]. This does not replace the need for basal insulin injections, but it could replace the meal time insulin requirements. Efficacy and safety data from a trial that included both type 1 and type 2 diabetic patients receiving inhaled insulin has shown equivalent glycaemic control to injected boluses of insulin. The main side effects of inhaled insulin are hypoglycaemia and throat pain.

New NICE guidelines
Formal guidelines for the management of type 2 diabetes are currently undergoing an update and have not yet been published. However, draft guidance documents do not suggest a paradigm shift in management strategies currently available. Although SGLT-2 inhibitors are mentioned, the place of these drugs and the newer concentrated insulins in the treatment algorithm of type 2 diabetes has not yet been fully elucidated.

Non-glycaemic approaches to type 2 diabetes
Although this article focuses on the pharmacological options for achieving optimal glycaemic control, the importance of patient education and supporting people to look after their own long term condition, through controlling blood pressure, lipids, smoking cessation and other cardiovascular risk factors, cannot be underestimated. There is evidence to suggest that lowering blood pressure significantly reduces diabetes related deaths, strokes, heart failure and microvascular complications. Angiotensin-converting enzyme inhibitors, such as ramipril, are preferred as first-line drugs because they limit the progression of renal damage. In comparison to glycaemic control, good blood pressure control does not show a ‘legacy effect’ and control must be maintained to preserve a benefit. NICE recommends that all patients should be offered a structured education programme to empower them to better understand and manage their condition.

As the incidence of type 2 diabetes rises along with the rate of diabetes complications, diabetes management must achieve good glycaemic control alongside optimal control of cardiovascular risk factors and empowering people to look after their own chronic condition. Such a multifaceted targeted approach is vital, not just to the individual but to the healthcare system as a whole. Although metformin, sulphonylureas and insulin will remain important drug choices for people with type 2 diabetes, newer drugs such as the GLP-1 agonists, DDP4 inhibitors and SGLT2 inhibitors and the newer insulin analogs provide an unique opportunity to target different underlying pathophysiological defects and are poised to play a larger role in the treatment paradigm of type 2 diabetes. Meanwhile, the expectation is that the new (revised) NICE guidelines can further guide, inform and improve this decision making process.