Severe Carbohydrate Restriction Research Articles

Type 1 diabetes: dietary modification over 100 years since insulin

AbstractDiet has been central for the management of type 1 diabetes for over three thousand years, and the discovery of insulin in 1921 was associated with the introduction of formal dietary education. Carbohydrate was soon identified as the macronutrient responsible for postprandial glucose excursions and over the past one hundred years, dietary interventions have alternated between severe carbohydrate restriction and so‐called free diets. The very low carbohydrate diets of the 1920s gave way to the free diets of the 1930s, and carbohydrate restriction was then reintroduced in the 1940s to the 1960s. In the 1970s, carbohydrate intake was increased with an emphasis on dietary fibre and low fat, healthy eating was recommended in the 1980s. The past few decades have reflected the growing evidence following the DCCT and DAFNE trials and dietary interventions are now individualised and emphasise carbohydrate counting and insulin adjustment and quality of life. Copyright © 2021 John Wiley & Sons.

SUN-003 Very Restricted Carbohydrate (Ketogenic) Diet: A Rare Cause of a Recurrent Hypoglycemic-Euglycemic Diabetic Ketoacidosis in the Pregnancy

Introduction: Although potential risk of DKA, ketogenic diet became popular among T1DM patients as proven to reduce the incidence of hypoglycemia, glycemic variability, and HbA1c (1).Severe carbohydrate restriction had not been included among DKA precipitating factors in pregnancy since a minimum consumption of 175 g of carbohydrates a day is recommended for pregnant women by the IOM and ADA.Proband: A 35-year-old pregnant woman (G2P1 at 29 weeks’ gestation) was admitted to the ICU because of a 12-hour history of severe nausea, 4 vomiting episodes (stomach contain), weakness, and metabolic acidosis accompanied by low normal BG values for pregnancy. She had a history of bulimia nervosa since 15 years of age that was well-controlled by severe carbohydrate restriction prior to pregnancy, and T1DM since 19 years of age. Her pre-pregnancy carbohydrate daily intake was ~ 20–30 g and BMI 24.1 kg/m2. Good glycemic control was established before conception and continued until delivery.Upon admission, she was tachypneic and suffering from diffuse abdominal pain. Fetal monitoring and abdominal ultrasonography showed no significant changes, and the sonographic fetal weight was appropriate for gestational age.The laboratory results revealed metabolic acidosis pH 7.23, bicarbonate 11.7 mmol/L, anion gap 22.5, and BG 78 mg/dL. Lactate and salicylate blood levels were normal. The blood β-hydroxybutyrate was highly positive and the patient was diagnosed with euglycemic DKA. She was managed with a continuous intravenous insulin infusion and fluid and electrolytes repletion.The patient was discharged after three days of hospitalization only to return four days later because of the similar complaints with findings of blood β-hydroxybutyrate 7.7 mmol/L and BG levels of 61–65 mg/dL. Because of persistent ketonemia with low normal BG levels, patient was questioning about her dietary habits and revealed to maintain severe carbohydrate-restricted pre-conception eating manners. After repeated consultations by specialists for eating disorder, patient agreed to increase her carbohydrate intake to 120 gr per day.Fetal brain MRI, fetal heart and brain ultrasound were performed to evaluate potential negative effects of ketones, and all were found normal. No major malformations were observed in the newborn, and a normal growth pattern was observed at 5 months of age.Conclusion: This is the first report of a pregnant T1DM patient with long lasting bulimia nervosa excellently controlled by severe carbohydrate restriction prior pregnancy and occultly continued against medical advice through the pregnancy, causing repeatedly hypoglycemic-euglycemic DKA.

SUN-176 Euglycemic Diabetic Ketoacidosis withSGLT2 Inhibitor Presenting as Chest Pain in a Patient with Coronary Artery Disease on a Ketogenic Diet

Background: Euglycemic diabetic ketoacidosis (DKA) is a known complication of sodium-glucose cotransporter 2 (SGLT2) inhibitors. We report an unusual case of euglycemic DKA caused by an SGLT2 inhibitor during self-introduction of a ketogenic diet; initial concern was for acute coronary syndrome. Clinical Case: A 61-year-old man with a history of type 2 diabetes with a hemoglobin A1c of 8.3%, coronary artery disease, hypertension, and hyperlipidemia presented to the emergency room with nausea and chest pain. The patient had a 30-year history of diabetes and was on oral therapy for years before starting insulin with an average daily dosage of 28 units. Three years ago, he started an SGLT2 inhibitor, improved his lifestyle and glycemic control, and was able to stop insulin. His home medications included empagliflozin 10 mg daily, metformin 500 mg twice a day, liraglutide 1.8 mg subcutaneously daily, rosuvastatin 5 mg daily, ezetimibe 10 mg daily, and omeprazole 40 mg daily. He reported several weeks of atypical chest pain and computed tomography angiography showed total occlusion of the mid-right coronary artery. He underwent an exercise stress test that showed echocardiographic changes that were positive for ischemia and subsequently was scheduled to undergo a left heart catheterization in 1 week. In the interim, he was highly motivated to change his lifestyle. He adopted a ketogenic diet, significantly limiting his daily carbohydrate. Five days later, he developed persistent and increased right-sided chest pain along with nausea, and presented to the emergency room. On review of systems, he reported hunger and his wife reported an odd breath odor. His vitals were stable. His troponin was negative and EKG showed inferior Q waves similar to prior EKGs. Given concern for acute coronary syndrome, he underwent cardiac catheterization, which showed the known complete total occlusion of RCA with collaterals, for which intervention was not performed. Review of additional labs showed: glucose 110 [70-100 mg/dL], bicarbonate 17 [22-29 mmol/L], anion gap 17 [6-14 mmol/L], betahydroxybutyric acid 4.1 [<0.3 mmol/L], large quantity of urinary ketones and glucose. He was diagnosed with euglycemic DKA and treated with insulin, fluids, and dextrose with resolution of ketoacidosis and chest pain. Conclusion: The use of SGLT2 inhibitors is increasingly favored in those with established cardiovascular disease, and carbohydrate-restrictive diets are a popular form of nutritional therapy. This case highlights severe carbohydrate restriction as an important risk factor that may predispose patients on SGLT2 inhibitors to euglycemic DKA that demonstrated with an unusual presentation of chest pain.

The ups and downs of low-carbohydrate diets in the management of Type 1 diabetes: a review of clinical outcomes.

Dietary management has been a mainstay of care in Type 1 diabetes since before the discovery of insulin when severe carbohydrate restriction was advocated. The use of insulin facilitated re-introduction of carbohydrate into the diet. Current management guidelines focus on a healthy and varied diet with consideration of glycaemic load, protein and fat. As a result of frustration with glycaemic outcomes, low-carbohydrate diets have seen a resurgence in popularity. To date, low-carbohydrate diets have not been well studied in the management of Type 1 diabetes. Studies looking at glycaemic outcomes from low-carbohydrate diets have largely been cross-sectional, without validated dietary data and with a lack of control groups. The participants have been highly motivated self-selected individuals who follow intensive insulin management practices, including frequent blood glucose monitoring and additional insulin corrections with tight glycaemic targets. These confounders limit the ability to determine the extent of the impact of dietary carbohydrate restriction on glycaemic outcomes. Carbohydrate-containing foods including grains, fruit and milk are important sources of nutrients. Hence, low-carbohydrate diets require attention to vitamin and energy intake to avoid micronutrient deficiencies and growth issues. Adherence to restricted diets is challenging and can have an impact on social normalcy. In individuals with Type 1 diabetes, adverse health risks such as diabetic ketoacidosis, hypoglycaemia, dyslipidaemia and glycogen depletion remain clinical concerns. In the present paper, we review studies published to date and provide clinical recommendations for ongoing monitoring and support for individuals who choose to adopt a low-carbohydrate diet. Strategies to optimize postprandial glycaemia without carbohydrate restriction are presented.

Carbohydrate restriction: Friend or foe of resistance-based exercise performance?

It is commonly accepted that adequate carbohydrate availability is necessary for optimal endurance performance. However, for strength- and physique-based athletes, sports nutrition research and recommendations have focused on protein ingestion, with far less attention given to carbohydrates. Varying resistance exercise protocols, such as differences in intensity, volume, and intraset rest prescriptions between strength-training and physique-training goals elicit different metabolic responses, which may necessitate different carbohydrate needs. The results of several acute and chronic training studies suggest that although severe carbohydrate restriction may not impair strength adaptations during a resistance training program, consuming an adequate amount of carbohydrate in the days leading up to testing may enhance maximal strength and strength-endurance performance. Although several molecular studies demonstrate no additive increases in postexercise mammalian target of rapamycin 1 phosphorylation with carbohydrate and protein compared with protein ingestion alone, the effects of chronic resistance training with carbohydrate restriction on muscle hypertrophy are conflicting and require further research to determine a minimal carbohydrate threshold necessary to optimize muscle hypertrophy. This review summarizes the current knowledge regarding carbohydrate availability and resistance training outcomes and poses new research questions that will better help guide carbohydrate recommendations for strength and physique athletes. In addition, given that success in physique sports is based on subjective appearance, and not objective physical performance, we also review the effects of subchronic carbohydrate ingestion during contest preparation on aesthetic appearance.

Characterizing the metabolic effects of exogenous ketone supplementation – an alternative or adjuvant to the ketogenic diet

The ketogenic diet (KD) is a high fat, adequate protein, low carbohydrate diet that has been used clinically to treat refractory pediatric epilepsy for nearly a century. Emerging evidence suggests that the KD is broadly neuroprotective and health‐promoting; therefore, it is now being investigated as a preventative strategy and/or treatment for a wide variety of disorders, including many neurological diseases, cancer, obesity, and diabetes, as well as for enhancing athletic performance and human resilience capabilities. Recently, studies have revealed that many of the beneficial effects associated with the KD are mechanistically attributable to the ketone bodies, leading our lab and others to develop and test exogenous ketone supplements (KS) which elevate blood ketones without the need for severe carbohydrate restriction. In order to further our understanding of this new technology, we sought to characterize the metabolic and physiologic effects, safety, and toxicity of KS in healthy rats. The KS tested included the R,S‐1,3‐butanediol acetoacetate diester, 1,3‐butanediol, medium chain triglyceride oil, caprylic acid, and beta‐hydroxybutyrate mineral salts, alone and in various combinations. Healthy rats were administered KS by oral gavage or in their food in an acute (once), sub‐chronic (1 month), or chronic (4 months) fashion, and were analyzed for a variety of metabolic and physiologic biomarkers. Acute and chronic KS rapidly elevated blood ketones to therapeutic levels (2–5mM) and simultaneously decreased blood glucose. Sub‐chronic KS treatment significantly altered the global metabolome. Medium chain fatty acids and dicarboxylic acids were elevated with KS treatment. Carnitine and deoxycarnitine was decreased with KS, while acetyl coA and acetylcarnitine were elevated, suggesting enhanced mitochondrial LCFA oxidation. Kreb's cycle intermediates, including citrate, succinate, and fumarate, were elevated with KS. The neurotransmitter adenosine was elevated with KS, while some purine nucleotide breakdown products were also elevated. Markers of both oxidative stress (oxidized glutathione) and antioxidant capacity (carnosine and anserine) were elevated by KS. Metabolites associated with the gut microbiome or nutrient absorption, such as indoleproprionate, 2‐hydroxyisobutyrate, and coprostanol, were altered. Inflammatory profiling following chronic KS administration revealed decreases in many pro‐inflammatory cytokines, including IL‐1β, IL‐6, IFN‐γ, MCP‐1, and RANTES. KS appears safe as there were no signs of toxicity or adverse changes in total cholesterol, HDL, LDL, triglycerides, or markers of liver/kidney function over the chronic treatment protocol. KS may be a useful alternative or adjuvant to the KD for disorders where nutritional ketosis is therapeutic.Support or Funding InformationThis work was supported by the Office of Naval Research grant N000140610105 and a charitable donation by Scivation, Inc.

Dor neuropática em paciente com porfiria: relato de caso

JUSTIFICATIVA E OBJETIVOS: As porfirias são um grupo de distúrbios herdados ou adquiridos que envolvem enzimas participantes do processo de síntese do heme. As manifestações agudas afetam o sistema nervoso, resultando em dor abdominal, vômitos, neuropatia aguda, convulsões e distúrbios mentais. A fisiopatogenia resulta do efeito tóxico dos precursores de porfirina, podendo ser desencadeada por fármacos usados de rotina na prática médica, restrição intensa de carboidratos e estresse metabólico. O objetivo deste trabalho foi apresentar um caso de porfiria de diagnóstico tardio, evoluindo para dor crônica. RELATO DO CASO: Paciente do sexo feminino, 27 anos, internada há 5 meses com dor abdominal intensa sem diagnóstico clínico. Foi indicada laparotomia exploradora, a qual não evidenciou causa para o quadro. A paciente, exposta a trauma cirúrgico e medicamentos que desencadeiam crise de porfiria, como cetoprofeno, metoclopramina e antibióticos, evoluiu com hiponatremia importante, elevação de enzimas hepáticas, convulsão e perda dos movimentos, sendo internada em Unidade de Terapia Intensiva. Após diagnóstico de porfiria, manteve dor em membros inferiores, sendo encaminhada para tratamento no Serviço de Dor da Santa Casa de Misericórdia de São Paulo. Iniciou tratamento com amitriptilina, gabapentina, opioide e analgésicos simples, mas continuou apresentando crises recorrentes da porfiria e, insegura quanto à condução do caso, abandonou o acompanhamento. CONCLUSÕES: A porfiria é um dos raros grupos de distúrbios enzimáticos que permanecem desconhecidos por grande parte dos profissionais de saúde. O paciente, ao perceber esse desconhecimento sobre a doença, tem seu nível de estresse e insegurança com o tratamento aumentado, dificultando a adesão e a continuidade ao mesmo.

Neuropathic Pain in a Patient with Porphyria. Case Report

Porphyrias represent a group of inherited or acquired disorders that involve enzymes that participate in heme synthesis. Acute manifestations affect the nervous system resulting in abdominal pain, vomiting, acute neuropathy, seizures, and mental disorders. The physiopathogeny results from the toxic effects of porphyrin precursors, and it can be triggered by drugs used routinely in medical practice, severe carbohydrate restriction, and metabolic stress. The objective of this report was to present the case of a late onset porphyria evolving to chronic pain. This is a 27 years old female who was admitted 5 months prior to her clinic appointment with severe abdominal pain without diagnosis. An exploratory laparotomy was indicated, which failed to demonstrate a cause for her pain. The patient was exposed to surgical trauma and drugs that can trigger porphyria, such as ketoprophen, metoclopramide, and antibiotics, and she evolved with significant hyponatremia, increased liver enzymes, seizures, and loss of movements that led to be admitted to the Intensive Care Unit. After the diagnosis of porphyria was made, the patient remained with pain in the lower limbs, being referred to the Pain Department of Santa Casa de Misericórdia de São Paulo. Treatment with amitriptyline, gabapentin, opioid, and simple analgesics was instituted; however, the patient continued to present recurring episodes of porphyria and, feeling insecure with the conduction of the case, she stopped the treatment. Porphyria is one of the rare groups of enzymatic disorders that remain unknown by the great majority of health professionals. Upon recognizing this lack of knowledge about the disease, the level of stress and insecurity of the patient increases hindering adhesion to and continuity of the treatment.

DIETARY CARBOHYDRATE AND METABOLISM OF INGESTED PROTEIN

Six normal people were fed a lean beef meal while on a normal diet and after seven days on a very low carbohydrate (<25 g/day) 2000 kcal/day diet. After carbohydrate restriction, the protein-induced rise in branched chain aminoacids was 40-50% greater than the rise after the control diet. Intravenous leucine also produced a 40% greater rise in plasma-leucine after carbohydrate restriction. Three days of fasting exaggerated protein-induced increases in plasma branched-chain aminoacids by 55-77%. Hypocaloric, pure carbohydrate refeeding restored the branched-chain aminoacid responses to normal. Severe carbohydrate restriction thus leads to increased accumulation of plasma branched-chain aminoacids after protein feeding which is at least in part due to reduced utilisation of these aminoacids.

Treatment of hyperlipidemias

The long-term effects of ethyl chlorophenoxyisobutyrate (CPIB), thyroid-active substances and diet were observed in seventy-two patients with five different types of hyperlipoproteinemias. Essential hypercholesterolemia (Sf 0–20 hyperlipoproteinemia) with tendon xanthomatosis proved refractory to CPIB, and to supplementary corn oil, but Sf 0–20 concentrations were reduced slightly (up to 20 per cent) by thyroid-active substances. Sf 0–20 hyperlipoproteinemia without tendon xanthomatosis was moderately reduced by CPIB or thyroid-active substances. In xanthoma tuberosum (characterized by very low Sf 0–12 and high Sf 12–400 lipoprotein concentrations), lipoprotein concentrations decreased to normal levels with severe carbohydrate restriction or (more acceptable to patients) CPIB therapy. In Sf 20–400 hyperlipoproteinemia, CPIB greatly reduced very low density lipoprotein, cholesterol and triglyceride levels but in 80 per cent of patients Sf 0–20 concentrations rose concurrently. In view of the atherogenicity of Sf 0–20 lipoproteins, if Sf 0–20 lipoprotein concentrations rise to high levels CPIB therapy should be discontinued. Carbohydrate restriction caused no consistent similar shift and appeared preferable to CPIB in this group. In combined Sf 0–20, Sf 20–400 hyperlipoproteinemia, CPIB reliably reduced Sf 20–400 levels; in some patients it decreased, and in some it increased Sf 0–20 concentrations; when increases occurred, added thyroid sometimes proved helpful.