Therapeutic employ of intermittent fasting and ketogenic diet equally an alternative treatment for blazon 2 diabetes in a normal weight woman: a 14-month case study

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  1. http://orcid.org/0000-0003-3166-1373Charlene Lichtash1,
  2. Jason Fung2,
  3. Katherine Connor Ostoich3 and
  4. Megan Ramos4
  1. 1 Section of Medicine, Cedars-Sinai Medical Center, Beverly Hills, California, USA
  2. 2 Section of Medicine, Scarborough Health Network, Scarborough, Ontario, Canada
  3. 3 National University of Republic of ireland Galway, Galway, Republic of ireland
  4. iv Plant of Kidney Life Science Technologies, Scarborough, Ontario, Canada
  1. Correspondence to Dr. Charlene Lichtash; charlene.lichtash{at}gmail.com

Abstract

This case demonstrates the effective and sustainable apply of intermittent fasting (IF) and ketogenic nutrition (KD) in a normal weight patient with type 2 diabetes, who did not attain glycaemic command with a standard care approach. A 57-year-one-time woman with blazon 2 diabetes treated with metformin and strict adherence to a standard diabetic diet presented with a haemoglobin A1c (HbA1c) of nine.3%. Within four months of transitioning to KD, combined with IF, she achieved glycaemic control off pharmacotherapy, with HbA1c of half dozen.four. IF regimens started every bit 24 hours three times per week, followed past 42 hours three times per week, then 42 hours two times per calendar week and 16 hours once per week. A maintenance phase was then begun at 8 months; IF was reduced to sixteen hours per day, with 24 hours three times per month, and metformin was restarted. At xiv months, HbA1c reached five.8%, and trunk mass index was minimally changed.

  • diabetes
  • general practice / family medicine
  • diet
  • endocrine arrangement

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  • diabetes
  • full general practice / family unit medicine
  • diet
  • endocrine system

Groundwork

Diabetes mellitus blazon 2 is a disease characterised by hyperglycaemia, varying levels of insulin resistance and impaired pancreatic beta-prison cell part. Both genetic and ecology factors contribute to the pathogenesis of blazon 2 diabetes.ane The growing epidemic of type 2 diabetes worldwide highlights the need for attainable preventative and therapeutic strategies. Co-ordinate to a global judge by the WHO in 2014, an estimated 422 meg adults were living with diabetes, with the prevalence of diabetes having doubled since 1980.2 In 2012, diabetes was the eighth leading cause of death amidst both sexes and the fifth leading crusade of expiry in women.2

Standard approaches to the treatment of type 2 diabetes incorporate lifestyle management, pharmacotherapy and occasionally bariatric surgery.3–v The goal of handling is euglycaemia and a reduction of the incidence of microvascular and macrovascular complications of type 2 diabetes. Medical nutrition therapy (MNT) is widely accepted every bit part of the standard of care in a diabetic patient.4 Guidelines cite several diets, including the Mediterranean diet, the Dietary Approaches to Stop Hypertension diet, vegetarian nutrition and low-carbohydrate diet, every bit effective in lowering haemoglobin A1c (HbA1c).4 Still, there is no consensus on the platonic macronutrient limerick of diet to reach command or remission of type ii diabetes.4 Ketogenic diets (KDs), which induce a country of nutritional ketosis (defined in the medical literature as a claret beta-hydroxybutyrate level of 0.5–3.0 mmol/L), have demonstrated effective reduction in HbA1c and metabolic parameters in patients with blazon 2 diabetes; however, studies are express in size and number.six–viii

Remission in blazon two diabetes has been demonstrated in large trials studying caloric restriction, also as bariatric surgery.9–11 While effective, bariatric surgery is limited by its accessibility, potential for complications and invasive nature. Caloric restriction is express by long-term patient adherence.12 Caloric restriction results in compensatory changes in the hormonal regulators of body weight, effectively reducing energy expenditure and increasing hunger.12 These changes accept been shown to persist for at least 12 months later implementing a calorie-restricted nutrition, explaining the claiming in applying this arroyo to the treatment of blazon 2 diabetes.12

By contrast, intermittent fasting (IF) is emerging as a potentially sustainable strategy to achieve control or remission of type 2 diabetes. Fasting is the voluntary abstinence from food, and IF is an eating regimen past which all meals are consumed within a strictly divers window of fourth dimension, followed by fasting.13 Some bachelor studies on IF use variations of fasting that let for the ingestion of fewer calories during this window, while others abstain from caloric intake altogether.xiii Patterns and lengths of fasting likewise vary among studies. Studies on the therapeutic use of IF in type 2 diabetes are very limited. Herein, we present a case of woman with type two diabetes who successfully used a combination of IF and a low-carbohydrate KD to attain glycaemic control.

While reduction of body weight is typically the goal of IF regimens, not all patients who suffer from type two diabetes are overweight. Many cases of blazon 2 diabetes amend or remit with weight loss, just the 2 goals are not the same. In this case, a alter in dietary pattern effectively controlled blazon 2 diabetes, although the patient was not overweight and overall weight change was minimal.

Instance presentation

A 57-yr-old woman with a 15-year history of type 2 diabetes had been managed for the bulk of her illness with metformin and a standard diabetic nutrition. She had a remote history of gestational diabetes at age xx and 34 years. At the time of her diagnosis with type 2 diabetes mellitus at age 42 years, her HbA1c was seven.1% and body mass index (BMI) was 21.9 kg/k2, classified as normal weight. During the course of her illness, she had strictly adhered to a diet prescribed to her by a registered dietician and based on prior American Diabetes Association (ADA) guidelines.fourteen It had consisted of carbohydrates from fruits, vegetables, whole grains, legumes and low-fatty dairy, likewise as poultry, fish and nuts. She had strictly limited her intake of saturated fat, red meats, sweets, sugar-sweetened beverages and sodium. She had regularly eaten 3 meals per day with two snacks.

In June 2016, at age 54 years, her HbA1c had risen to 8.7% and BMI to 23.2 kg/thousand², while on metformin and her diabetic diet; glipizide was then added to her regimen. By Feb 2017, her HbA1c had only marginally improved to eight.iii%, but she experienced weight gain with a rise in her BMI to 24%, a common side effect of sulfonylurea drugs. Pioglitazone was afterward added to her regimen of metformin and glipizide, but she reported not taking it consistently due to episodes of hypoglycaemia and dizziness. In June 2017, her HbA1c was 7.8%, and she was told to lower her dose of glipizide, continue metformin and to resume pioglitazone. In Oct 2017, her HbA1c had improved to six.v%; notwithstanding, she reported frequent hypoglycaemia, dizziness and feeling unwell, and she discontinued her pioglitazone and glipizide on her own. In July 2018, her HbA1c had risen to nine.iii% on a regimen of metformin and her diabetic diet.

Handling

In July 2018, she began strictly following a KD, followed by the initiation of an IF regimen ii weeks later on. The KD, a low-carbohydrate high-fat (LCHF) diet, consisted of the following macronutrient composition: 80% fat, 15% protein and 5% carbohydrates. The nutrition focused on eating natural, unprocessed fats containing a multifariousness of monounsaturated and polyunsaturated sources. Protein was predominantly from pasture-raised chicken and eggs, grass-fed beef and wild-caught fish. Grains, starches, legumes and the majority of fruits were eliminated, with almost of the carbohydrates in the diet consisting of leafy greens and raw or fermented vegetables. Total daily consumption was estimated to be 20–30 g of carbohydrates and 1500 calories. She reported eating to satiety, without strictly measuring calories.

IF was started at 24 hours three times per week on Monday, Wednesday and Friday. After 2 weeks, she increased the duration of fasting to 42 hours three times per week, which she connected for 4 months. Because of the significant improvement in blood glucose, and the lack of bachelor information to guide the choice of a follow-upwards regimen, she then reduced her fasting to 42 hours on Mondays and Wednesdays, and xvi hours on Fridays for 4 months. In an effort to examination the need for continued 42 hours fasts, a maintenance phase was then started, during which fasting was reduced to 16 hours per twenty-four hour period and 24 hours three times per month for 6 months. Metformin thousand mg ii times per day was reinitiated at the beginning of the maintenance phase. When non fasting, she ate two meals per day with no boosted snacks betwixt meals. On days she fasted 24 hours, she ate 1 meal per twenty-four hours. During fasts she drank h2o, manifestly tea or coffee and occasionally bootleg bone goop.

Outcome and follow-up

4 weeks afterwards initiating her dietary changes, the patient discontinued all medications, including metformin, an antihypertensive and a statin, while at the same fourth dimension significantly improving glycaemic control. A timeline and summary of the patient's diabetic medications with wellness parameters recorded at each visit are displayed in table one. HbA1c dropped past ii.9%, from nine.3% to 6.4% during the first 4 months of dietary treatment, as depicted in figure 1. A few hypoglycemic episodes were noted only when initiating the IF regimen, but none subsequently. Her HbA1c at eight months was 6.4%, at which time, fasting insulin, postprandial insulin rising and C peptide were all at the lower stop of normal range. At this point, when glycaemic control had been achieved, metformin was added. At xiv months, HbA1c was reduced to 5.8. The patient'southward weight and BMI were mildly reduced, equally demonstrated in effigy 2, with her most contempo weight and BMI being 53.5 kg and 21.half-dozen kg/grand2, respectively. When fasting, she recorded ketone levels at 0.5–ane mmol/L using a commercial blood ketone monitor, confirming nutritional ketosis. During the get-go 8 days after initiating KD, the patient reported mild fatigue and headache. These cocky-limited symptoms are mutual when starting a KD and are oft referred to colloquially as keto influenza. Thereafter, she reported no difficulties in maintaining the nutrition and fasting regimen, and she noted an improvement in her free energy level, do tolerance and quality of life. Despite tolerating the 42 hours fasting periods without difficulty, she reported greater satisfaction with her fasting regimen in the maintenance phase, citing a greater sense of normalcy when able to engage in daily meals. The patient currently continues with her KD and IF, which she plans to maintain indefinitely.

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Table 1

Timeline of patient treatment modality for type 2 diabetes and measured health parameters

Nosotros present a case of a normal weight patient with uncontrolled blazon 2 diabetes despite adherence to oral hypoglycemic medications and standard dietary communication, who successfully managed her condition using a relatively novel lifestyle approach, combining IF with a KD. The therapeutic benefits of IF and KD in the management of blazon 2 diabetes are reported in the medical literature, but they accept non been studied in large scale. Their use is guided predominately by an understanding of their proposed pathophysiologic mechanisms reported in animal data, and by outcomes reported in limited man data.

Studies on IF generally demonstrate its effectiveness in improving glycaemic command and other metabolic parameters, including reduction in visceral fatty, blood pressure and markers of oxidative stress and inflammation.13 xv–xx The bachelor human data for IF prove marked benefit in pre-diabetes and type 2 diabetes. In a instance report of iii patients with long-standing blazon ii diabetes each requiring at least 70 units of insulin per mean solar day, the implementation of 24 hours fasts either three times per calendar week or on alternate days, combined with a recommended low-carbohydrate nutrition resulted in the complete discontinuation of insulin in all 3 patients; reductions in HbA1c, BMI and waist circumference were besides demonstrated.17 Moreover, the benefits of IF on insulin sensitivity extend beyond its influence on weight loss. A contempo trial in men with pre-diabetes and overweight or obesity showed that 5 weeks of an IF regimen improved insulin sensitivity and pancreatic beta-prison cell responsiveness, independent of weight loss.xx Another study comparing caloric restriction to an IF regimen for weight loss showed a greater increase in insulin sensitivity when using an IF strategy.21 The findings in our case mirror those in the literature; IF was an effective and sustainable tool for achieving glycaemic command and reducing the need for pharmacotherapy in our patient, independent of weight loss.

Animal data advise a mechanistic understanding of the effects of IF on glycaemic control, providing hope that this handling modality may ho-hum or reverse the progression of type 2 diabetes. Mice fed a fasting-mimicking diet showed an increase in the proliferation and number of insulin-generating pancreatic beta cells in late-stage type 2 diabetes.22 Differentiated cells in the pancreas first decreased in number in the fasted state, and then pancreatic transitional cells and beta cells proliferated in the refed country.22 This study suggests that the therapeutic benefit of IF lies in the combined physiologic effects caused by both the fasted state, and past the recovery menstruation during the feeding stage, to promote beta-prison cell repair. Another study in mice showed increased pancreatic beta-cell mass using IF.23 Glucose stimulated insulin secretion increased and beta-cell apoptosis decreased.23 Additionally, weight loss was not required for the benefits of IF on pancreatic beta-cell survival and role.23 The possibility that IF can promote pancreatic beta cells to regenerate and has the potential to revolutionise our handling of type 2 diabetes, currently viewed as a chronic progressive disease. Further man studies are needed to help illuminate the potential role IF may have in slowing or reversing this disease.

The processes linking IF and benefits in insulin sensitivity are currently existence studied to help with targeted pharmacologic therapy that can mimic effects of IF. One such area of ongoing enquiry is in the sirtuin proteins, a family unit of enzymes with regulatory effects on glucose homeostasis, fat metabolism and life span regulated by both nutrient levels and calorie brake.xviii 19 In detail, sirtuin-6 (SIRT6) is currently being studied as a potential therapeutic target for treating insulin resistance.24 SIRT6 in brute studies enhances insulin sensitivity and thereby decreases fasting blood glucose levels.24–26 Both brusk-term fasting and long-term calorie brake increment SIRT6 levels in animal information farther highlighting the role IF may play in illness modification19

Sugar brake is considered an effective treatment of type 2 diabetes in standard MNT, equally defined by the ADA and the European Association for the Study of Diabetes.4 This approach even predates the evolution of exogenous insulin treatment in 1921, and is based on the fact that carbohydrates are the macronutrient with the highest glycaemic and insulin indices.27 An increased carbohydrate intake worsens markers of insulin resistance, such as postprandial glucose and insulin levels.28 Several trials accept demonstrated improvements in HbA1c and insulin sensitivity when implementing a low-sugar diet.29 The benefits of dietary carbohydrate restriction on control of blood glucose do not necessarily require weight loss, and low-carbohydrate diets take been shown to be generally well tolerated.30 31

While the benefits of low-carbohydrate diets in type 2 diabetes are well accepted, the role of KD in the management of type 2 diabetes is not widely accepted at the present time, partly due to express long-term safe information. A KD is typically defined equally a LCHF diet that induces a shift in energy source from glucose to fatty acids and fatty-acid-derived ketones. Achieving nutritional ketosis has been shown to result in diabetes remission and reversal in some cases.8 A non-randomised long-term study implementing KD plant significant improvements in biomarkers, including HbA1c, weight, fasting glucose, fasting insulin, blood pressure, cholesterol profile, high sensitivity C-reactive protein and a reduced need for type 2 diabetic medication.6 By contrast, the command arm consisting of patients with type 2 diabetes receiving 'usual care' with counselling on lifestyle interventions by a registered dietitian showed no significant change in whatsoever of the biomarkers measured.6

However, in other affliction states, both KDs and IF accept a long history of safety. KD was first used in the 1920s in the treatment of epilepsy.32 During virtually a century of clinical use, in that location have been remarkably few wellness concerns. IF has been used fifty-fifty longer in the treatment of epilepsy, having been described by the ancient Greek md Hippocrates more than than 2400 years ago.33 Further, IF has been a traditional function of virtually every major faith in the world.

Our patient tolerated the KD well, with her only reported difficulty being the week-long initial flow of adjustment, termed in popular media equally keto flu and in the medical literature every bit keto induction.34 Common symptoms of keto flu include influenza-similar symptoms, headache, fatigue, nausea, dizziness, gastrointestinal discomfort and decreased energy.34 The symptoms tend to peak within the starting time 7 days of initiating a KD and resolve inside the offset month.34 While data show that IF and the product of ketone bodies consequence in adaptive responses that influence health and longevity, further inquiry on KDs is needed to help support their widespread apply in the treatment of diabetes mellitus.

IF and a low-carbohydrate nutrition, such as a KD, appear to be specially effective when used in combination. These two dietary interventions address different just complementary parts of the total diet. A KD specifies which foods should or should non exist eaten (what to consume), but does not give guidance on the timing of meals (when to eat). IF provides guidance on the meal timing merely not meal composition. Together they provide a consummate dietary solution that each lacks on its own.

The time to achieving glycaemic command in blazon 2 diabetes with this combined approach varies, and further studies are needed to define the determining factors, such as degree of insulin resistance and pancreatic beta-cell reserve. Our patient accomplished glycaemic control inside iv months of combining KD and IF. Another study plant that in three patients with insulin-dependent diabetes, implementation of IF and a low-carbohydrate diet resulted in discontinuation of insulin between v and 18 days of initiating treatment.17 For maintenance of glycaemic control, the duration and degree of IF and carbohydrate restriction must also be tailored to the individual patient. As demonstrated in our case, one time glycaemic control was accomplished the lengths of fasts were able to be reduced, without compromising glycaemic control. Further studies should help identify patient characteristics that predict ideal fasting lengths and saccharide limits in the management of type 2 diabetes.

The available information on KD and IF is encouraging, and our case report and review of the literature highlights the need for more extensive research on these two handling modalities in the treatment of blazon 2 diabetes. With the alarming rise in incidence of blazon ii diabetes worldwide, the need for cost-effective and widely available strategies to manage this affliction is growing. The need for pharmacotherapy and invasive bariatric surgery tin can be effectively lowered through the use of our approach. Further, every bit shown in animal and preliminary human data, the strategies we discussed in our written report have the potential to modify the course of type 2 diabetes, which has long been understood as a chronic progressive illness. If validated in large-scale randomised studies, the current data on both IF and KD have the potential to revolutionise our agreement of the pathophysiology of blazon ii diabetes and profoundly impact the standard arroyo to treatment of this affliction.

Learning points

  • The apply of intermittent fasting (IF) and a ketogenic diet (KD) is an constructive and sustainable alternative to a standard care approach in the treatment of blazon ii diabetes.

  • IF and a KD can be used in a patient with type 2 diabetes who is normal weight. Glycaemic control can exist achieved without resulting in significant weight loss.

  • The use of this dietary strategy minimises or eliminates the demand for pharmacotherapy, and it may exist superior to a standard care approach to type 2 diabetes.

  • We demonstrate adept adherence to a strategy of IF and a KD in a patient who could non tolerate the adverse furnishings of boosted oral hypoglycemic medications when nether a standard care approach.

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