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Cited by 48Diabetes Management and ResearchPancreatic function and diabetesDiabetes Treatment and Management

Postprandial Reactive Hypoglycemia

Open access
Altuntaş, Yüksel·2019·SiSli Etfal Hastanesi Tip Bulteni / The Medical Bulletin of Sisli Hospital
DOI 10.14744/semb.2019.59455PMC PMC7192270
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Abstract

Postprandial Reactive Hypoglycemia R eactive hypoglycemia (RH) is the condition of postpran- dially hypoglycemia occurring 2-5 hours after food intake.[1] Many conditions are associated with postprandial hypoglycemia.RH clinically seen in three different forms as follows: idiopathic RH (at 180 min), alimentary (within 120 min) and late RH (at 240-300 min).Earliest change before type 2 diabetes is the loss of first-phase insulin release, which emerges with fasting glucose levels of about 110 mg/dl.Lack of first-phase insulin release, an excellent predictor of both types of diabetes, is thought to be the earliest sign of the adverse effects of hyperglycemia on beta-cells and insulin-sensitive tissues.[2] When the first-phase insulin response decreases, firstly, blood glucose starts to rise after the meal, which leads to late but excessive secretion of the second-phase insulin secretion.Thus, late reactive hypoglycemia occurs.[3] Elevated insulin levels also cause downregulation of the insulin postreceptor on the muscle and fat cells, thus decreasing insulin sensitivity.The cause of the increase in insulin sensitivity in IRH at 3 h is not completely clear.However, there is a decrease in insulin sensitivity in late reactive hypoglycaemia at 4 or 5 hours.Thus, patients with hypoglycemia at 4 or 5 h who have those with a higher number of people with diabetes in the first-degree relative and who have obesity may be more susceptible to diabetes Reactive hypoglycemia (RH) is the condition of postprandially hypoglycemia occurring 2-5 hours after food intake.RH is clinically seen in three different forms as follows: idiopathic RH (at 180 min), alimentary (within 120 min), and late RH (at 240-300 min).When the first-phase insulin response decreases, firstly, blood glucose starts to rise after the meal.This leads to late but excessive secretion of the second-phase insulin secretion.Thus, late reactive hypoglycemia occurs.Elevated insulin levels also cause down-regulation of the insulin post-receptor on the muscle and fat cells, thus decreasing insulin sensitivity.The cause of the increase in insulin sensitivity in IRH at 3 h is not completely clear.However, there is a decrease in insulin sensitivity in late reactive hypoglycaemia at 4 or 5 hours.Thus, patients with hypoglycemia at 4 or 5 h who have a family history of diabetes and obesity may be more susceptible to diabetes than patients with hypoglycemia at 3 h.We believe that some cases with normal glucose tolerance in OGTT should be considered as prediabetes at <55 or 60 mg/dl after 4-5 hours after OGTT.Metformin and AGI therapy may be recommended if there is late RH with IFG.Also Metformin, AGİ, TZD, DPP-IVInhibitors, GLP1RA therapy may be recommended if there is late RH with IGT.As a result, postprandial RH (<55 or 60 mg/dl ), especially after 4 hours may predict diabetes.Therefore, people with RH along with weight gain and with diabetes history in the family will benefit from a lifestyle modification as well as the appropriate antidiabetic approach in the prevention of diabetes.

AI snapshot

Written from the paper’s full text.

TL;DR

Reactive hypoglycemia (RH) is postprandial hypoglycemia occurring 2–5 hours after food intake, with idiopathic, alimentary, and late forms. The paper argues that late RH, especially after 4–5 hours, may predict diabetes and should prompt lifestyle and antidiabetic approaches in at-risk patients.

Key findings

  • RH is clinically divided into idiopathic RH (at 180 min), alimentary RH (within 120 min), and late RH (at 240–300 min); diagnosis of hypoglycemia requires blood sugar ≤55 mg/dL, though symptoms can occur without reaching this threshold (postprandial syndrome).
  • Loss of first-phase insulin release, emerging at fasting glucose around 110 mg/dL, leads to late but excessive second-phase insulin secretion and late reactive hypoglycemia; elevated insulin also down-regulates insulin post-receptor signaling on muscle and fat cells, decreasing insulin sensitivity.
  • Prediabetes carries high diabetes risk: 5–10% of prediabetics per year progress to type 2 diabetes, combined IFG+IGT confers a 2-fold greater risk than either alone, and approximately 70% of prediabetic patients followed for life become diabetic later.
  • Suggested therapy: for IFG plus postprandial RH, metformin and AGI; for IGT plus postprandial RH, metformin, AGI, TZD, DPP-IV inhibitors, and GLP1RA. Incretins account for 50–70% of total insulin secreted after oral glucose in non-diabetic subjects, but the incretin effect contributes only 20–35% of the insulin response in type 2 diabetes.

Methods

  • Narrative review; no systematic review methods, databases, inclusion criteria, or primary sample are stated in the paper.
  • The paper synthesizes prior literature on the pathophysiology, diagnosis, and treatment of postprandial reactive hypoglycemia, including prediabetes, insulin resistance, beta-cell dysfunction, incretins, and pharmacologic approaches.
  • Main analysis is thematic discussion of cited studies and author recommendations; no formal meta-analysis or original data analysis is reported.

Limitations

  • Stated: the cause of increased insulin sensitivity in idiopathic RH at 3 hours is not completely clear, and the cause and pathophysiological importance of idiopathic postprandial RH have not been fully elucidated.
  • Stated: OGTT and mixed meal tests are described as suboptimal for RH diagnosis because they can show false-positive and false-negative results, respectively.
  • Evident: as a narrative review without systematic search or quality appraisal, treatment recommendations and risk predictions rely on cited studies and author opinion rather than a formal evidence synthesis.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.14744/semb.2019.59455

Cites

51 of 51 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

24 of 64 cited sources checked · 6 supported · 1 flagged · accuracy not yet measured

  • Premisecitation

    In early period of type 2 diabetes and in IGT, first-phase insulin secretion declines.

    “In the early period of type 2 diabetes and in IGT, the first-phase insulin secretion declines with the loss.[8, 9]”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [8] Wasada T Kuroki H Katsumori K Arii H Sato A Aoki K Who are more insulin resistant, people with IFG or people with IGT? Diabetologia 2004 47 758 9 15298356 source

      In the results discussion (page not available), the paper reports that early-phase insulin secretion was lower in the IFG group, not the IGT group, although the difference was not significant. Its conclusion says people with IGT show a compensatory increase in insulin secretion. The study does not examine people with early type 2 diabetes. (LLM, conf=0.83)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
    • cites [9] Pimenta WP Santos ML Cruz NS Aragon FF Padovani CR Gerich JE Brazilian individuals with impaired glucose tolerance are characterized by impaired insulin secretion Diabetes Metab 2002 28 468 76 12522327
  • Premisecitation

    Patients with normal glucose tolerance and 1-hour blood glucose ≥155 mg/dl on OGTT have more diabetes risk than impaired fasting glucose.

    “It has also been reported that patients with normal glucose tolerance and 1-hour blood glucose ≥155 mg/dl on OGTT cause more diabetes risk than impaired fasting glucose.[13]”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [13] Fiorentino TV Marini MA Andreozzi F Arturi F Succurro E Perticone M One-Hour Postload Hyperglycemia Is a Stronger Predictor of Type 2 Diabetes Than Impaired Fasting Glucose J Clin Endocrinol Metab 2015 100 3744 51 26274345 source
  • Interpretationcitation

    There is a definite beta-cell defect in IFG and IGT.

    “These results demonstrate a definite beta-cell defect in IFG and IGT.[21]”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [21] Kanat M Mari A Norton L Winnier D DeFronzo RA Jenkinson C Distinct β-cell defects in impaired fasting glucose and impaired glucose tolerance Diabetes 2012 61 447 53 22275086 PMC3266412 source
  • Premisecitation

    In non-diabetic subjects, incretins are responsible for 50-70% of total insulin secreted after oral glucose.

    “In non-diabetic subjects, Incretins are responsible for 50–70% of the total insulin secreted after oral glucose administration.[23–25]”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [23] De León DD Crutchlow MF Ham JY Stoffers DA Role of glucagon-like peptide-1 in the pathogenesis and treatment of diabetes mellitus Int J Biochem Cell Biol 2006 38 845 59 16202636 source
    • cites [24] Kim W Egan JM The role of incretins in glucose homeostasis and diabetes treatment Pharmacol Rev 2008 60 470 512 19074620 PMC2696340 source

      The Background and Introduction states that the incretin effect accounts for at least 50% of insulin secreted after oral glucose. This supports the lower end of the claim, but the passage does not establish a 70% upper bound; no page number is available in our copy. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [25] Campbell JE Drucker DJ Pharmacology, physiology, and mechanisms of incretin hormone action Cell Metab 2013 17 819 37 23684623 source
  • Premisecitation

    Cardiovascular mortality is significantly increased in prediabetic patients compared to patients with normal blood glucose.

    “Cardiovascular mortality is also significantly increased in prediabetic patients compared to patients with normal blood glucose.[14, 15]”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [14] Ford ES Zhao G Li C Pre-diabetes and the risk for cardiovascular disease:a systematic review of the evidence J Am Coll Cardiol 2010 55 1310 7 20338491 source

      The Results (page unavailable) report significantly elevated pooled risks for cardiovascular disease outcomes with impaired fasting glucose and impaired glucose tolerance. But the review pools cardiovascular disease outcomes rather than establishing a separate, statistically significant increase in cardiovascular mortality; its combined IFG/IGT estimate also has a confidence interval spanning 1. The claim is therefore more specific and categorical than the reported findings. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [15] Festa A D'Agostino R Jr Hanley AJ Karter AJ Saad MF Haffner SM Differences in insulin resistance in nondiabetic subjects with isolated impaired glucose tolerance or isolated impaired fasting glucose Diabetes 2004 53 1549 55 15161760 source
  • Classified as probably not a substantial claim. 5
  • May combine two claims. 18

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Every year 5-10% of prediabetics turn into open type 2 diabetics and return to normoglycemia.

    “Every year 5-10% of the prediabetics turn into open type 2 diabetics and return to normoglycemia.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [10] Tabák AG Herder C Rathmann W Brunner EJ Kivimäki M Prediabetes:a high-risk state for diabetes development Lancet 2012 379 2279 90 22683128 PMC3891203 source

      The Progression from prediabetes to diabetes section states that around 5–10% of people with prediabetes become diabetic annually. The Reversion to normoglycaemia section says prediabetes can also revert, but does not establish a 5–10% annual reversion rate. These are alternative outcomes for different people, not a sequence in which the same people become diabetic and return to normoglycaemia. (LLM, conf=0.79)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Elevated insulin levels cause down-regulation of insulin post-receptor on muscle and fat cells, decreasing insulin sensitivity.

    “Elevated insulin levels also cause down-regulation of the insulin postreceptor signals on the muscle and fat cells, thus decreases insulin sensitivity.[6]”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [6] Mandarino L Baker B Rizza R Genest J Gerich J Infusion of insulin impairs human adipocyte glucose metabolism in vitro without decreasing adipocyte insulin receptor binding Diabetologia 1984 27 358 63 6389241 source

      The Abstract reports that insulin infusion reduced adipocyte glucose metabolism without reducing adipocyte insulin binding, and the Discussion interprets this as an initial post-receptor defect causing insulin resistance. The Discussion also mentions earlier in-vitro findings in rat myoblasts, but this study did not test muscle cells or demonstrate down-regulation of specific post-receptor signals. Those parts of the claim are more specific than the evidence supports. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    When first-phase insulin response decreases, blood glucose rises after meal, leading to late but excessive second-phase insulin secretion, causing late reactive hypoglycemia.

    “When the first-phase insulin response decreases, firstly, blood glucose starts to rise after the meal, which leads to late but excessive secretion of the second-phase insulin secretion. Thus, late reactive hypoglycemia occurs.[3]”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [3] Mitrakou A Kelley D Mokan M Veneman T Pangburn T Reilly J Role of reduced suppression of glucose production and diminished early insulin release in impaired glucose tolerance N Engl J Med 1992 326 22 9 1727062 source

      The Discussion (pp. 6–7) links diminished early insulin release to a larger rise in glucose after ingestion and suggests that the resulting hyperglycemia stimulates delayed hyperinsulinemia. It does not identify this as excessive second-phase secretion or say that it causes late reactive hypoglycemia. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Loss of first-phase insulin secretion and decreased second-phase insulin secretion are characteristic features of type 2 diabetes.

    “Loss of first-phase insulin secretion and decreased second-phase insulin secretion are characteristic features of type 2 diabetes.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [8] Wasada T Kuroki H Katsumori K Arii H Sato A Aoki K Who are more insulin resistant, people with IFG or people with IGT? Diabetologia 2004 47 758 9 15298356 source

      The results passage (page not provided) reports a more pronounced defect in early insulin response in people with impaired fasting glucose than in those with impaired glucose tolerance. It does not establish loss of first-phase secretion in people with type 2 diabetes, and a search for second-phase secretion found no passage addressing it. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
    • cites [9] Pimenta WP Santos ML Cruz NS Aragon FF Padovani CR Gerich JE Brazilian individuals with impaired glucose tolerance are characterized by impaired insulin secretion Diabetes Metab 2002 28 468 76 12522327

  • May combine two claims.

    Premisecitation

    Previous prospective randomized trials have shown lifestyle modifications and pharmacological agents significantly reduce risk of developing Type 2 DM and cardiovascular risk factors in prediabetic patients.

    “Previous prospective randomized trials have shown that lifestyle modifications and pharmacological agents significantly reduce the risk of developing Type 2 DM and cardiovascular risk factors in prediabetic patients.[16]”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [16] Godsland IF Jeffs JAR Johnston DG Loss of beta cell function as fasting glucose increases in the non-diabetic range Diabetologia 2004 47 1157 66 15249997 source

      The Design section describes an observational cohort analysis of fasting glucose and insulin responses, not a randomized intervention trial. The Introduction discusses diabetes risk, but our copy does not report whether lifestyle changes or pharmacological agents reduce diabetes incidence or cardiovascular risk factors in prediabetic patients. Searches for lifestyle interventions, drugs, and prevention trials found no supporting passage; page numbers were not available. (LLM, conf=0.76)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Low-dose glitazones given to patients with reactive hypoglycemia associated with IGT are considered effective in symptoms of reactive hypoglycaemia and prevention of diabetes.

    “Low-dose glitazones given to patients with reactive hypoglycemia associated with IGT are also considered to be effective in the symptoms of reactive hypoglycaemia and the prevention of diabetes.[39, 40]”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [39] Luo Y Paul SK Zhou X Chang C Chen W Guo X Rationale, Design, and Baseline Characteristics of Beijing Prediabetes Reversion Program:A Randomized Controlled Clinical Trial to Evaluate the Efficacy of Lifestyle Intervention and/or Pioglitazone in Reversion to Normal Glucose Tolerance in Prediabetes J Diabetes Res 2017 2017 7602408 28168204 PMC5266841 source

      The Discussion (page unavailable) reports that thiazolidinediones can prevent or delay progression from impaired glucose tolerance to diabetes. It does not address relief of reactive hypoglycaemia symptoms or establish effectiveness specifically in patients with reactive hypoglycaemia. The Methods specify pioglitazone at 30 mg/day but do not characterize it as a low dose. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [40] Espinoza SE Wang CP Tripathy D Clement SC Schwenke DC Banerji MA Pioglitazone is equally effective for diabetes prevention in older versus younger adults with impaired glucose tolerance Age (Dordr) 2016 38 485 93 27585671 PMC5266219 source

      The Results (Effect of treatment on conversion to diabetes; page unavailable) report that pioglitazone reduced diabetes incidence in adults with impaired glucose tolerance. But the Methods (Study design; page unavailable) specify 30 mg/day, increased to 45 mg/day as tolerated; the paper does not establish effectiveness of low-dose treatment or report improvement in reactive hypoglycaemia symptoms. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Pathophysiologic-based therapy is associated with marked improvement in glucose tolerance and reversion of prediabetes to normal glucose tolerance in more than 50% of patients.

    “It has been suggested that pathophysiologic- based therapy is associated with marked improvement in glucose tolerance and reversion of prediabetes to normal glucose tolerance in more than 50% of patients.[44-47]”
    Quote in the paperNot a substantial claim2 of 4 sources checked
    • cites [44] Rosenstock J Foley JE Rendell M Landin-Olsson M Holst JJ Deacon CF Effects of the dipeptidyl peptidase-IV inhibitor vildagliptin on incretin hormones, islet function, and postprandial glycemia in subjects with impaired glucose tolerance Diabetes Care 2008 31 30 5 17947341 source
    • cites [45] Kaku K Kadowaki T Terauchi Y Okamoto T Sato A Okuyama K Sitagliptin improves glycaemic excursion after a meal or after an oral glucose load in Japanese subjects with impaired glucose tolerance Diabetes Obes Metab 2015 17 1033 41 26094974 PMC5034821 source

      The Results > Efficacy section reports improved glucose responses with sitagliptin and, in a post hoc analysis, a return to normal blood glucose in 53.2% of the 50 mg group after seven weeks. But the 25 mg group reached 47.6%, and this short study in Japanese subjects with impaired glucose tolerance does not establish the claim for pathophysiologic-based therapy generally. (LLM, conf=0.89)

      Experimental — accuracy not yet measured
    • cites [46] Hemmingsen B Sonne DP Metzendorf MI Richter B Dipeptidyl-peptidase (DPP)-4 inhibitors and glucagon-like peptide (GLP)-1 analogues for prevention or delay of type 2 diabetes mellitus and its associated complications in people at increased risk for the development of type 2 diabetes mellitus Cochrane Database Syst Rev 2017 5 CD012204 28489279 PMC6481586 source

      The review’s discussion of the SCALE trial reports improved glucose tolerance and regression to normoglycaemia in 970/1472 (66%) participants receiving liraglutide after 160 weeks, versus 36% receiving placebo. That supports the improvement and more-than-50% figure for liraglutide, but not for pathophysiologic-based therapy generally; the review also reports 50% normoglycaemia after 12 weeks off treatment. No page number is available in our copy. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [47] İbrahim M Tuomilehto J Aschner P Beseler L Cahn A Eckel RH Global status of diabetes prevention and prospects for action:A consensus statement Diabetes Metab Res Rev 2018 34 e3021 29757486 source

  • May combine two claims.

    Premisecitation

    Sitagliptin treatment for 7-8 weeks resulted in reductions in post-challenge glucose excursions during both MTT and OGTT in Japanese subjects with IGT, increased early insulin response to glucose load during OGTT, and reduced circulating glucagon levels during MTT.

    “Sitagliptin treatment for 7–8 weeks resulted in reductions in post-challenge glucose excursions during both an MTT and an OGTT, in Japanese subjects with IGT. The observation that treatment with sitagliptin increased the early insulin response to the glucose load during the OGTT, and reduced circulating glucagon levels during the MTT.[45]”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [45] Kaku K Kadowaki T Terauchi Y Okamoto T Sato A Okuyama K Sitagliptin improves glycaemic excursion after a meal or after an oral glucose load in Japanese subjects with impaired glucose tolerance Diabetes Obes Metab 2015 17 1033 41 26094974 PMC5034821 source

  • May combine two claims.

    Premisecitation

    Individuals with IFG have insulin sensitivity close to normal in muscle with severe hepatic insulin resistance in liver, whereas individuals with IGT have moderate insulin resistance in liver but severe insulin resistance in muscle.

    “Individuals with IFG have insulin sensitivity close to normal/normal in the muscle with severe hepatic insulin resistance in the liver whereas individuals with IGT have moderate insulin resistance in the liver, but severe insulin resistance in the muscle.[9, 15-19]”
    Quote in the paperSubstantial claim2 of 6 sources checked
    • cites [9] Pimenta WP Santos ML Cruz NS Aragon FF Padovani CR Gerich JE Brazilian individuals with impaired glucose tolerance are characterized by impaired insulin secretion Diabetes Metab 2002 28 468 76 12522327
    • cites [15] Festa A D'Agostino R Jr Hanley AJ Karter AJ Saad MF Haffner SM Differences in insulin resistance in nondiabetic subjects with isolated impaired glucose tolerance or isolated impaired fasting glucose Diabetes 2004 53 1549 55 15161760 source
    • cites [16] Godsland IF Jeffs JAR Johnston DG Loss of beta cell function as fasting glucose increases in the non-diabetic range Diabetologia 2004 47 1157 66 15249997 source

      The Results report no marked trend in overall insulin sensitivity across categories of deteriorating glucose homeostasis, but do not separate sensitivity in muscle from resistance in the liver. The Discussion notes that some participants may have had impaired glucose tolerance, without comparing IFG and IGT on tissue-specific insulin resistance. Searches for hepatic and muscle insulin resistance did not locate the claimed comparison. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [17] Altuntas Y Bilir M Ucak S Gundogdu S Reactive hypoglycemia in lean young women with PCOS and correlations with insulin sensitivity and with beta cell function Eur J Obstet Gynecol Reprod Biol 2005 119 198 205 15808380 source
    • cites [18] Weyer C Bogardus C Pratley RE Metabolic characteristics of individuals with impaired fasting glucose and/or impaired glucose tolerance Diabetes 1999 48 2197 203 10535454 source
    • cites [19] Meyer C Pimenta W Woerle HJ Van Haeften T Szoke E Mitrakou A Different mechanisms for impaired fasting glucose and impaired postprandial glucose tolerance in humans Diabetes Care 2006 29 1909 14 16873801 source

      The Hyperglycemic clamp discussion says IFG may involve preferential hepatorenal insulin resistance with normal or near-normal muscle sensitivity, while IGT may involve preferential muscle resistance. It does not establish the claimed severe-versus-moderate degrees: it describes IGT hepatorenal sensitivity as normal or near-normal, and the Abstract reports only an approximately 15% decrease in clamp-determined sensitivity for IGT. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    First phase insulin secretion is significantly reduced in both IFG and IGT, while second phase insulin secretion is only reduced in IGT.

    “A recent study showed that the first phase insulin secretion was significantly reduced in both IFG and IGT, while the second phase insulin secretion was only reduced in IGT.[10, 20]”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [10] Tabák AG Herder C Rathmann W Brunner EJ Kivimäki M Prediabetes:a high-risk state for diabetes development Lancet 2012 379 2279 90 22683128 PMC3891203 source

      The section on differences between isolated IFG and IGT says early insulin response is impaired in both groups, while late-phase secretion is impaired in IGT but improves in IFG. This supports the phase-specific pattern, but the paper reports findings from cited studies rather than presenting itself as the original study, and the passage does not state statistical significance. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [20] van Haeften TW Pimenta W Mitrakou A Korytkowski M Jenssen T Yki-Jarvinen H Disturbances in beta-cell function in impaired fasting glycemia Diabetes 2002 51 Suppl 1 S265 70 11815491 source

  • May combine two claims.

    Premisecitation

    Both IFG and IGT have insulin resistance and beta-cell defect.

    “Both IFG and IGT have both insulin resistance and beta-cell defect.”
    Quote in the paperSubstantial claim2 of 6 sources checked
    • cites [9] Pimenta WP Santos ML Cruz NS Aragon FF Padovani CR Gerich JE Brazilian individuals with impaired glucose tolerance are characterized by impaired insulin secretion Diabetes Metab 2002 28 468 76 12522327
    • cites [15] Festa A D'Agostino R Jr Hanley AJ Karter AJ Saad MF Haffner SM Differences in insulin resistance in nondiabetic subjects with isolated impaired glucose tolerance or isolated impaired fasting glucose Diabetes 2004 53 1549 55 15161760 source
    • cites [16] Godsland IF Jeffs JAR Johnston DG Loss of beta cell function as fasting glucose increases in the non-diabetic range Diabetologia 2004 47 1157 66 15249997 source

      The Results (page unavailable) show declining first-phase insulin secretion as glucose homeostasis deteriorated, supporting the beta-cell-defect component. They report no marked trend in insulin sensitivity, however, and the Discussion (page unavailable) says participants were not classified by impaired glucose tolerance (IGT). The paper therefore does not establish that both IFG and IGT have both defects. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [17] Altuntas Y Bilir M Ucak S Gundogdu S Reactive hypoglycemia in lean young women with PCOS and correlations with insulin sensitivity and with beta cell function Eur J Obstet Gynecol Reprod Biol 2005 119 198 205 15808380 source
    • cites [18] Weyer C Bogardus C Pratley RE Metabolic characteristics of individuals with impaired fasting glucose and/or impaired glucose tolerance Diabetes 1999 48 2197 203 10535454 source
    • cites [19] Meyer C Pimenta W Woerle HJ Van Haeften T Szoke E Mitrakou A Different mechanisms for impaired fasting glucose and impaired postprandial glucose tolerance in humans Diabetes Care 2006 29 1909 14 16873801 source

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationreasoning

    Occurring late postprandially hypoglycemia with family history of diabetes, even if lean, should be considered at potential risk of diabetes in the future in patients with late RH.

    “Occurring late postprandially hypoglycemia with a family history of diabetes, even if they are lean, should be considered at potential risk of diabetes in the future in patients with late RH.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Neither OGTT nor mixed meal test is suitable for diagnosis of RH because they show false-positive and false-negative results, respectively.

    “Neither the OGTT nor the mixed meal test is really a suitable this diagnosis because they show false-positive and false-negative results, respectively.[7]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [7] Charles MA Hofeldt F Shackelford A Waldeck N Dodson LE Jr Bunker D Comparison of oral glucose tolerance tests and mixed meals in patients with apparent idiopathic postabsorptive hypoglycemia:absence of hypoglycemia after meals Diabetes 1981 30 465 70 7227659 source

  • May combine two claims.

    Premisecitation

    In alimentary RH, rapid gastric emptying and increased plasma GLP-1 levels precede RH after oral glucose loading in gastrectomy patients.

    “In alimentary RH, rapid gastric emptying and increased plasma GLP-1 levels precede RH after oral glucose loading in gastrectomy patients,[4]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [4] Gebhard B Holst JJ Biegelmayer C Miholic J Postprandial GLP-1, norepinephrine, and reactive hypoglycemia in dumping syndrome Dig Dis Sci 2001 46 1915 23 11575444 source

  • May combine two claims.

    Premisecitation

    Lack of first-phase insulin release is an excellent predictor of both types of diabetes and is thought to be the earliest sign of adverse effects of hyperglycemia on beta-cells and insulin-sensitive tissues.

    “Lack of first-phase insulin release, an excellent predictor of both types of diabetes, is thought to be the earliest sign of the adverse effects of hyperglycemia on beta-cells and insulin-sensitive tissues.[2]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [2] Poitout V Robertson RP An integrated view of beta-cell dysfunction in type-II diabetes Annu Rev Med 1996 47 69 83 8712804 source

  • May combine two claims.

    Premisecitation

    Idiopathic RH may arise from high insulin sensitivity, probably most frequently (50-70%), which is not measured by indices of insulin sensitivity.

    “RH may arise from an increased insulin response, which might be related either to insulin resistance or to increased GLP-1, renal glycosuria, defects in glucagon response, or high insulin sensitivity probably the most frequently (50–70%), which is not be measured by indices of insulin sensitivity.[5]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [5] Leonetti F Foniciello M Iozzo P Riggio O Merli M Giovannetti P Increased nonoxidative glucose metabolism in idiopathic reactive hypoglycemia Metabolism 1996 45 606 10 8622604 source

  • May combine two claims.

    Premisecitation

    Early reactive hypoglycemia may be due to accelerated gastric emptying or exaggerated incretin effect.

    “It may be due to accelerated gastric emptying, or exaggerated incretin effect.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] Brun JF Fedou C Mercier J Postprandial reactive hypoglycemia Diabetes Metab 2000 26 337 51 11119013

  • May combine two claims.

    Premisecitation

    In type 2 diabetes patients, incretin effect is impaired and contributes to 20-35% of insulin response to oral glucose.

    “The incretin effect is impaired and contributes to 20-35% of the insulin response to oral glucose, in type 2 diabetes patients.[26]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [26] Holst JJ The physiology of glucagon-like peptide 1 Physiol Rev 2007 87 1409 39 17928588 source

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    Some cases with normal glucose tolerance in OGTT or cases with IGT criteria in OGTT should be considered as prediabetes at <55 mg/dl after 3 hours after OGTT is extended to 4 or 5 hours.

    “We believe that some cases with normal glucose tolerance in OGTT or cases with IGT criteria in OGTT should be considered as prediabetes at <55 mg/dl after 3 hours after OGTT is extended to 4 or 5 hours.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Ma-Pi 2 diet reduced blood glucose excursions during the day, facilitating glycemic control in subjects with RH.

    “The macrobiotic Ma-Pi 2 diet reduced blood glucose excursions during the day, thereby facilitating glycemic control in subjects with RH.[48, 49]”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [48] Quercia S Turroni S Fiori J Soverini M Rampelli S Biagi E Gut microbiome response to short-term dietary interventions in reactive hypoglycemia subjects Diabetes Metab Res Rev 2017 33 28806487 source
    • cites [49] Soare A Khazrai YM Fontana L Del Toro R Lazzaro MC Di Rosa C Treatment of reactive hypoglycemia with the macrobiotic Ma-pi 2 diet as assessed by continuous glucose monitoring:The MAHYP randomized crossover trial Metabolism 2017 69 148 56 28285645 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    GLP-1 may be involved in pathogenesis of idiopathic reactive hypoglycemia without prediabetes.

    “Lupoli et al. Suggests that GLP-1 may be involved in the pathogenesis of idiopathic reactive hypoglycemia without prediabetes.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] Lupoli R Cotugno M Griffo E Nosso G Riccardi G Capaldo B Role of the Entero-Insular Axis in the Pathogenesis of Idiopathic Reactive Hypoglycemia:A Pilot Study J Clin Endocrinol Metab 2015 100 4441 6 26502359 source
21 of 21

  • The paper relies on this without support.

    Interventions effective in prediabetes (lifestyle modification and antidiabetic agents) are effective in preventing diabetes in people with reactive hypoglycemia.

    “Therefore, people with reactive hypoglycaemia along with weight gain and, with diabetes history in the family will benefit from a lifestyle modification as well as the appropriate antidiabetic approach in the prevention of diabetes.”

  • The paper relies on this without support.

    The clinical forms of reactive hypoglycemia (idiopathic, alimentary, late) are distinct and correspond to the stated timing.

    “RH clinically seen in three different forms as follows: idiopathic RH (at 180 min), alimentary (within 120 min) and late RH (at 240–300 min).”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Thresholds such as <70 mg/dL are commonly used in practice, although more stringent cutoff values (e.g., <54 mg/dL) are considered for defining clinically significant episodes.

    “Thresholds such as <70 mg/dL are commonly used in practice, although more stringent cutoff values (e.g., <54 mg/dL) are considered for defining clinically significant episodes [6,10].”

    From Defining and Characterizing Postprandial Reactive Hypoglycemia (2026) · cites this paper as [10]

    The section on incretins and beta-cell dysfunction (page unavailable) says diagnosis of hypoglycemia requires blood sugar of 55 mg/dL or less, broadly supporting a more stringent cutoff near 54 mg/dL. Our copy does not say that <70 mg/dL is commonly used in practice or distinguish it from a cutoff for clinically significant episodes (searched: 70 mg/dL, 54 mg/dL, diagnostic thresholds). (LLM, conf=0.78)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Late hypoglycemia extends beyond the stated RH window

    Minor

    Reactive hypoglycemia is defined as occurring 2-5 hours after food intake, whereas a later passage says late postprandial hypoglycemia occurs at 4-6 hours.

  • Late reactive hypoglycemia begins at different stated times

    Minor

    The paper initially defines late reactive hypoglycemia as occurring at 240-300 minutes (4-5 hours), but later says it occurs from the 3rd through 5th hour.

2 of 2

Cites

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1 of the 52 references couldn’t be matched to a known paper.

Cited by

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Related

Authors
Altuntaş, Y.
Affiliations
Sağlık Bilimleri Üniversitesi (TR)
Corresponding author
Altuntaş, Yüksel
ORCID
Altuntaş, Yüksel
Venue
SiSli Etfal Hastanesi Tip Bulteni / The Medical Bulletin of Sisli Hospital
Publisher
Kare Publishing
Published
2019
Volume
53
Issue
3
Pages
215-220
ISSN
1302-7123 (ISSN-L)
DOI
10.14744/semb.2019.59455
PMC
PMC7192270
OpenAlex
W2955166198
Semantic Scholar
745bda370e6432e105cf4ebf4d2b2538be77eb55
Cited by
47
References
52
Citations by year
2026: 4 · 2025: 6 · 2024: 6 · 2023: 7 · 2022: 10 · 2021: 11 · 2020: 1 · 2018: 2
FWCI
3.79
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • SiSli Etfal Hastanesi Tip Bulteni / The Medical Bulletin of Sisli Hospital (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nc)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords
reactive hypoglycemia, postprandial hypoglycemia, first-phase insulin secretion, second-phase insulin secretion, insulin resistance, insulin receptor down-regulation, type 2 diabetes risk, beta-cell dysfunction, hyperglycemia, obesity, family history of diabetes

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-14.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-14.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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